Long terminal repeats act as androgen-responsive enhancers for the PSA-Kallikrein locus

The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to individual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units

Anatomical MR imaging of long bones : comparative performance of MRI at 1.5 T and 3 T

The current gold standard for the design of orthopaedic implants is 3D models of long bones obtained using computed tomography (CT). However, high-resolution CT imaging involves high radiation exposure, which limits its use in healthy human volunteers. Magnetic resonance imaging (MRI) is an attractive alternative for the scanning of healthy human volunteers for research purposes. Current limitations of MRI include difficulties of tissue segmentation within joints and long scanning times. In this work, we explore the possibility of overcoming these limitations through the use of MRI scanners operating at a higher field strength. We quantitatively compare the quality of anatomical MR images of long bones obtained at 1.5 T and 3 T and optimise the scanning protocol of 3 T MRI. FLASH images of the right leg of five human volunteers acquired at 1.5 T and 3 T were compared in terms of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The comparison showed a relatively high CNR and SNR at 3 T for most regions of the femur and tibia, with the exception of the distal diaphyseal region of the femur and the mid diaphyseal region of the tibia. This was accompanied by an ~65% increase in the longitudinal spin relaxation time (T1) of the muscle at 3 T compared to 1.5 T. The results suggest that MRI at 3 T may be able to enhance the segmentability and potentially improve the accuracy of 3D anatomical models of long bones, compared to 1.5 T. We discuss how the total imaging times at 3 T can be kept short while maximising the CNR and SNR of the images obtained.

Timing and emplacement dynamics of newly recognised mass flow deposits at ~ 8–12 ka offshore Soufrière Hills volcano, Montserrat : how submarine stratigraphy can complement subaerial eruption histories

This contribution describes two mass movement deposits (total volume ~0.5 km3) identified in seven marine cores located 8 to 15 km offshore southern Montserrat, West Indies. The deposits were emplaced in the last 35 ka and have not previously been recognised in either the subaerial or distal submarine records. Age constraints, provided by radiocarbon dating, show that an explosive volcanic eruption occurred at ca 8–12 ka, emplacing a primary eruption-related deposit that overlies a large (~0.3 km3) reworked bioclastic and volcaniclastic flow deposit, formed from a shelf collapse between 8 and 35 ka. The origin of these deposits has been deduced through the correlation of marine sediment cores, component analysis and geochemical analysis. The 8–12 ka primary volcanic deposit was likely derived from a highly-erosive pyroclastic flow from the Soufrière Hills volcano that entered the ocean and mixed with the water column forming a water-supported density current. Previous investigations of the eruption record suggested that there was a hiatus in activity at the Soufrière Hills volcano between 16 and 6 ka. The ca 8–12 ka eruptive episode identified here shows that this hiatus was shorter than previously hypothesised, and thus highlights the importance of obtaining an accurate and completemarine record of events offshore from volcanic islands and incorporating such data into eruption history reconstructions. Comparisons with the submarine deposit characteristics of the 2003 dome collapse also suggests that the ~8–12 ka eruptive episode was more explosive than eruptions from the current eruptive episode.

Novel keratins identified by quantitative proteomic analysis as the major cytoskeletal proteins of equine (Equus caballus) hoof lamellar tissue

The dermo-epidermal interface that connects the equine distal phalanx to the cornified hoof wall withstands great biomechanical demands, but is also a region where structural failure often ensues as a result of laminitis. The cytoskeleton in this region maintains cell structure and facilitates intercellular adhesion, making it likely to be involved in laminitis pathogenesis, although it is poorly characterized in the equine hoof lamellae. The objective of the present study was to identify and quantify the cytoskeletal proteins present in the epidermal and dermal lamellae of the equine hoof by proteomic techniques. Protein was extracted from the mid-dorsal epidermal and dermal lamellae from the front feet of 5 Standardbred geldings and 1 Thoroughbred stallion. Mass spectrometry-based spectral counting techniques, PAGE, and immunoblotting were used to identify and quantify cytoskeletal proteins, and indirect immunofluorescence was used for cellular localization of K14 and K124 (where K refers to keratin). Proteins identified by spectral counting analysis included 3 actin microfilament proteins; 30 keratin proteins along with vimentin, desmin, peripherin, internexin, and 2 lamin intermediate filament proteins; and 6 tubulin microtubule proteins. Two novel keratins, K42 and K124, were identified as the most abundant cytoskeletal proteins (22.0 ± 3.2% and 23.3 ± 4.2% of cytoskeletal proteins, respectively) in equine hoof lamellae. Immunoreactivity to K14 was localized to the basal cell layer, and that to K124 was localized to basal and suprabasal cells in the secondary epidermal lamellae. Abundant proteins K124, K42, K14, K5, and α1-actin were identified on 1- and 2-dimensional polyacrylamide gels and aligned with the results of previous studies. Results of the present study provide the first comprehensive analysis of cytoskeletal proteins present in the equine lamellae by using mass spectrometry-based techniques for protein quantification and identification.

Morphometry and abnormalities of the feet of Kaimanawa feral horses in New Zealand

Objective: The present study investigated the foot health of the Kaimanawa feral horse population and tested the hypotheses that horses would have a large range of foot morphology and that the incidence of foot abnormality would be significantly high. Procedures: Abnormality was defined as a variation from what the two veterinarian assessors considered as optimal morphology and which was considered to impact negatively on the structure and/or function of the foot. Fifteen morphometric variables were measured on four calibrated photographic views of all four feet of 20 adult Kaimanawa feral horses. Four morphometric variables were measured from the lateromedial radiographs of the left forefoot of each horse. In addition, the study identified the incidence of gross abnormality observed on the photographs and radiographs of all 80 feet. Results: There was a large variation between horses in the morphometric dimensions, indicating an inconsistent foot type. Mean hoof variables were outside the normal range recommended by veterinarians and hoof care providers; 35% of all feet had a long toe conformation and 15% had a mediolateral imbalance. Abnormalities included lateral (85% of horses) and dorsal (90% of horses) wall flares, presence of laminar rings (80% of horses) and bull-nose tip of the distal phalanx (75% of horses). Both hypotheses were therefore accepted. Conclusions: The Kaimanawa feral horse population demonstrated a broad range of foot abnormalities and we propose that one reason for the questionable foot health and conformation is lack of abrasive wearing by the environment. In comparison with other feral horse populations in Australia and America there may be less pressure on the natural selection of the foot of the Kaimanawa horses by the forgiving environment of the Kaimanawa Ranges. Contrary to popular belief, the feral horse foot type should not be used as an ideal model for the domestic horse foot.

A new model to study healing of a complex femur fracture with concurrent soft tissue injury in sheep

High energy bone fractures resulting from impact trauma are often accompanied by subcutaneous soft tissue injuries, even if the skin remains intact. There is evidence that such closed soft tissue injuries affect the healing of bone fractures, and vice versa. Despite this knowledge, most impact trauma studies in animals have focussed on bone fractures or soft tissue trauma in isolation. However, given the simultaneous impact on both tissues a better understanding of the interaction between these two injuries is necessary to optimise clinical treatment. The aim of this study was therefore to develop a new experimental model and characterise, for the first time, the healing of a complex fracture with concurrent closed soft tissue trauma in sheep. A pendulum impact device was designed to deliver a defined and standardised impact to the distal thigh of sheep, causing a reproducible contusion injury to the subcutaneous soft tissues. In a subsequent procedure, a reproducible femoral butterfly fracture (AO C3-type) was created at the sheep’s femur, which was initially stabilised for 5 days by an external fixator construct to allow for soft tissue swelling to recede, and ultimately in a bridging construct using locking plates. The combined injuries were applied to twelve sheep and the healing observed for four or eight weeks (six animals per group) until sacrifice. The pendulum impact led to a moderate to severe circumferential soft tissue injury with significant bruising, haematomas and partial muscle disruptions. Posttraumatic measurements showed elevated intra-compartmental pressure and circulatory tissue breakdown markers, with recovery to normal, pre-injury values within four days. Clinically, no neurovascular deficiencies were observed. Bi-weekly radiological analysis of the healing fractures showed progressive callus healing over time, with the average number of callus bridges increasing from 0.4 at two weeks to 4.2 at eight weeks. Biomechanical testing after sacrifice showed increasing torsional stiffness between four and eight weeks healing time from 10% to 100%, and increasing ultimate torsional strength from 10% to 64% (relative to the contralateral control limb). Our results demonstrate the robust healing of a complex femur fracture in the presence of a severe soft tissue contusion injury in sheep and demonstrate the establishment of a clinically relevant experimental model, for research aimed at improving the treatment of bone fractures accompanied by closed soft tissue injuries.

The acute transverse strain response of the patellar tendon to quadriceps exercise

Introduction: The human patellar tendon is highly adaptive to changes in habitual loading but little is known about its acute mechanical response to exercise. This research evaluated the immediate transverse strain response of the patellar tendon to a bout of resistive quadriceps exercise. Methods: Twelve healthy adult males (mean age 34.0+/-12.1 years, height 1.75+/-0.09 m and weight 76.7+/-12.3 kg) free of knee pain participated in the research. A 10-5 MHz linear-array transducer was used to acquire standardised sagittal sonograms of the right patellar tendon immediately prior to and following 90 repetitions of a double-leg parallel-squat exercise performed against a resistance of 175% bodyweight. Tendon thickness was determined 20-mm distal to the pole of the patellar and transverse Hencky strain was calculated as the natural log of the ratio of post- to pre-exercise tendon thickness and expressed as a percentage. Measures of tendon echotexture (echogenicity and entropy) were also calculated from subsequent gray-scale profiles. Results: Quadriceps exercise resulted in an immediate decrease in patellar tendon thickness (P<.05), equating to a transverse strain of -22.5+/-3.4%, and was accompanied by increased tendon echogenicity (P<.05) and decreased entropy (P<.05). The transverse strain response of the patellar tendon was significantly correlated with both tendon echogenicity (r = -0.58, P<.05) and entropy following exercise (r=0.73, P<.05), while older age was associated with greater entropy of the patellar tendon prior to exercise (r=0.79, P<.05) and a reduced transverse strain response (r=0.61, P<.05) following exercise. Conclusions: This study is the first to show that quadriceps exercise invokes structural alignment and fluid movement within the matrix that are manifest by changes in echotexture and transverse strain in the patellar tendon., (C)2012The American College of Sports Medicine

Emplacement of pyroclastic deposits offshore Montserrat : insights from 3D seismic data

During the current (1995-present) eruptive phase of the Soufrière Hills volcano on Montserrat, voluminous pyroclastic flows entered the sea off the eastern flank of the island, resulting in the deposition of well-defined submarine pyroclastic lobes. Previously reported bathymetric surveys documented the sequential construction of these deposits, but could not image their internal structure, the morphology or extent of their base, or interaction with the underlying sediments. We show, by combining these bathymetric data with new high-resolution three dimensional (3D) seismic data, that the sequence of previously detected pyroclastic deposits from different phases of the ongoing eruptive activity is still well preserved. A detailed interpretation of the 3D seismic data reveals the absence of significant (> 3. m) basal erosion in the distal extent of submarine pyroclastic deposits. We also identify a previously unrecognized seismic unit directly beneath the stack of recent lobes. We propose three hypotheses for the origin of this seismic unit, but prefer an interpretation that the deposit is the result of the subaerial flank collapse that formed the English's Crater scarp on the Soufrière Hills volcano. The 1995-recent volcanic activity on Montserrat accounts for a significant portion of the sediments on the southeast slope of Montserrat, in places forming deposits that are more than 60. m thick, which implies that the potential for pyroclastic flows to build volcanic island edifices is significant.

Identification and occupational stress : a stress-buffering perspective

Occupational stress research has consistently demonstrated many negative effects of work stressors on employee adjustment (i.e., job-related attitudes and health). Considerable literature also describes potential moderators of this relationship. While research has revealed that different workplace identifications can have significant positive effects on employee adjustment, it has neglected to investigate their potential stress-buffering effects. Based on identity theories, it was predicted that stress-buffering effects of different types of identifications (distal versus proximal) would be revealed when the identification type and employee adjustment outcome type (distal versus proximal) were congruent. Predictions were tested with an employee sample from five human service nonprofit organizations (N = 337). Hierarchical multiple regression analyses revealed that main and moderated effects relating to identification supported the notion that occupational stress would be reduced when there was congruence of distal and proximal identifications and distal and proximal outcome types. However, stress-buffering effects were also found for high identifiers and low identifiers that were not in line with hypotheses posing questions for the definitions of distal and proximal identifications. Findings are discussed in terms of theoretical and practical implications.

Two cycles of voluminous pyroclastic volcanism and sedimentation related to episodic granite emplacement during the late Archean : Eastern Yilgarn Craton, Western Australia

The thick piles of late-Archean volcaniclastic sedimentary successions that overlie the voluminous greenstone units of the eastern Yilgarn Craton, Western Australia, record the important transition from the cessation in mafic-ultramafic volcanism to cratonisation between about 2690 and 2655 Ma. Unfortunately, an inability to clearly subdivide the superficially similar sedimentary successions and correlate them between the various geological terranes and domains of the eastern Yilgarn Craton has led to uncertainty about the timing and nature of the region's palaeogeographic and palaeotectonic evolution. Here, we present the results of some 2025 U–Pb laser-ablation-ICP-MS analyses and 323 Sensitive High-Resolution Ion Microprobe (SHRIMP) analyses of detrital zircons from 14 late-Archean felsic clastic successions of the eastern Yilgarn Craton, which have enabled correlation of clastic successions. The results of our data, together with those compiled from previous studies, show that the post-greenstone sedimentary successions include two major cycles that both commenced with voluminous pyroclastic volcanism and ended with widespread exhumation and erosion associated with granite emplacement. Cycle One commences with an influx of rapidly reworked feldspar-rich pyroclastic debris. These units, here-named the Early Black Flag Group, are dominated by a single population of detrital zircons with an average age of 2690–2680 Ma. Thick (up to 2 km) dolerite bodies, such as the Golden Mile Dolerite, intrude the upper parts of the Early Black Flag Group at about 2680 Ma. Incipient development of large granite domes during Cycle One created extensional basins predominantly near their southeastern and northwestern margins (e.g., St Ives, Wallaby, Kanowna Belle and Agnew), into which the Early Black Flag Group and overlying coarse mafic conglomerate facies of the Late Black Flag Group were deposited. The clast compositions and detrital-zircon ages of the late Black Flag Group detritus match closely the nearby and/or stratigraphically underlying successions, thus suggesting relatively local provenance. Cycle Two involved a similar progression to that observed in Cycle One, but the age and composition of the detritus were notably different. Deposition of rapidly reworked quartz-rich pyroclastic deposits dominated by a single detrital-zircon age population of 2670–2660 Ma heralded the beginning of Cycle Two. These coarse-grained quartz-rich units, are name here the Early Merougil Group. The mean ages of the detrital zircons from the Early Merougil Group match closely the age of the peak in high-Ca (quartz-rich) granite magmatism in the Yilgarn Craton and thus probably represent the surface expression of the same event. Successions of the Late Merougil Group are dominated by coarse felsic conglomerate with abundant volcanic quartz. Although the detrital zircons in these successions have a broad spread of age, the principal sub-populations have ages of about 2665 Ma and thus match closely those of the Early Merougil Group. These successions occur most commonly at the northwestern and southeastern margins of the granite batholiths and thus are interpreted to represent resedimented units dominted by the stratigraphically underlying packages of the Early Merougil Group. The Kurrawang Group is the youngest sedimentary units identified in this study and is dominated by polymictic conglomerate with clasts of banded iron formation (BIF), granite and quartzite near the base and quartz-rich sandstone units containing detrital zircons aged up to 3500 Ma near the top. These units record provenance from deeper and/or more-distal sources. We suggest here that the principal driver for the major episodes of volcanism, sedimentation and deformation associated with basin development was the progressive emplacement of large granite batholiths. This interpretation has important implication for palaeogeographic and palaeotectonic evolution of all late-Archean terranes around the world.

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated.

Mice lacking β-Adrenergic receptors have increased bone mass but are not protected from deleterious skeletal effects of ovariectomy

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling.

Localization of fibronectin in the rat testis : effects of serum and dibutyryl cyclic AMP on fibronectin deposition by peritubular myoid cells in culture

The peritubular zone of the rat testis has an extensive extracellular matrix (ECM). Fibronectin (FN) is distributed primarily in the basal lamina of the seminiferous tubule boundary tissue and is synthesized by peritubular myoid cells. Several extracellular changes are mediated by growth factors and these changes occur at the time of hormone mediated testicular development, particularly in the peritubular zone. The effects of serum or dibutyryl cyclic AMP (cAMP) on FN production by the mesenchymal peritubular myoid cells were evaluated. Rats of various ages (10, 15, 20, 40 and 80 days) were employed for immunofluorescent localization of rat testicular FN in frozen sections. In all age groups tested, FN was primarily present in a broad layer around each seminiferous tubule, and blood vessel, and in variable distribution throughout the interstitial stroma. By day 20 there was no clear distinction in FN staining between the peritubular zone and the interstitial tissue. This indicates an involvement of FN in the ECM developments which occur in the peritubular zone of the testis at this time. The peritubular myoid cells were isolated from 20-22 day old rat testis and cultured on glass coverslips. These cells were grown to confluence with 10% fetal calf serum (FCS) in medium until day 4 and then subcultured to have secondary monocultures maintained with or without serum. By means of immunofluorescence and cytochemistry using avidin-biotin peroxidase complex it was observed that peritubular myoid cells were positive for FN and most of the FN was localized in the perinuclear region. Subcultured peritubular myoid cells maintained for 4 days in medium containing FCS developed an extensive interconnecting FN matrix. In the presence of 0.5 mM cAMP in culture, FN became localized along the filamentous process of peritubular myoid cells and more prominently in the areas of triangulated multi-cell aggregates as well as on the surface of the contracted small spherical cells. The addition of cAMP in the presence of FCS, also caused a noticeable change in the staining pattern; FN was detected along the filamentous process developing into a complex network of cells encased in an extensive matrix. It would appear that the translocation of FN in the cytoplasmic extensions of peritubular myoid cells may be a direct consequence of morphological changes associated with metabolic regulation of cAMP. This may also be related to the puberty associated development of in vivo changes in the ECM produced by peritubular myoid cells.

Novel use of faecal sterols to assess human faecal contamination in Antarctica : a likelihood assessment matrix for environmental monitoring

Wastewater containing human sewage is often discharged with little or no treatment into the Antarctic marine environment. Faecal sterols (primarily coprostanol) in sediments have been used for assessment of human sewage contamination in this environment, but in situ production and indigenous faunal inputs can confound such determinations. Using gas chromatography with mass spectral detection profiles of both C27 and C29 sterols, potential sources of faecal sterols were examined in nearshore marine sediments, encompassing sites proximal and distal to the wastewater outfall at Davis Station. Faeces from indigenous seals and penguins were also examined. Faeces from several indigenous species contained significant quantities of coprostanol but not 24-ethylcoprostanol, which is present in human faeces. In situ coprostanol and 24-ethylcoprostanol production was identified by co-production of their respective epi isomers at sites remote from the wastewat er source and in high total organic matter sediments. A C 29 sterols-based polyphasic likelihood assessment matrix for human sewage contamination is presented, which distinguishes human from local fauna faecal inputs and in situ production in the Antarctic environment. Sewage contamination was detected up to 1.5 km from Davis Station.

Regulation of microRNA-1288 in colorectal cancer : altered expression and its clinicopathological significance

We aim to examine the miR-1288 expression in cancer cell lines and a large cohort of patients with colorectal cancer. Two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The miRNA expressions of miR-1288 were tested on these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). An exogenous miR-1288 (mimic) was used to detect cell proliferation and cell cycle changes in SW480 using MTT calorimetric assay and flow cytometry, respectively. In addition, tissues from 122 patients with surgical resection of colorectum (82 adenocarcinomas, 20 adenomas, and 20 non-neoplastic tissues) were tested for miR-1288 expression by qRT-PCR. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Over expression of miR-1288 in SW480 cell line showed increased cell proliferation and increased G2-M phase cells. In tissues, reduced miR-1288 expression was noted in majority of colorectal adenocarcinoma compared to colorectal adenoma and non-neoplastic tissues. Reduced or absent expression of miR-1288 was noted in 76% (n = 62/82) of the cancers. The expression levels of miR-1288 were higher in distal colorectal adenocarcinomas (P = 0.013) and in cancers of lower T staging (P = 0.033). To conclude, alternation of miR-1288 expression is important in the progression of colorectal cancer. The differential regulation of miR-1288 was found to be related to cancer location and pathological staging in colorectal cancers.