miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: significance of their regulation

Recently, we reported a functional interaction between miR-21 and its identified chemokine target CCL20 in colorectal cancer (CRC) cell lines. Here, we investigated whether such functional interactions are permitted at the cellular level which would require an inverse correlation of expression and also co-expression of miR-21 and CCL20 in the same cell. Expression profiling was performed using qPCR, and ELISA, in situ hybridization and immunohistochemistry were applied for the presentation of their cellular localization. We demonstrated that miR-21 as well as CCL20 were both significantly upregulated in CRC tissues; thus, showing no antidromic expression pattern. This provided an initial clue that miR-21 and CCL20 may not be expressed in the same cell. In addition, we located miR-21 expression at the cellular level predominantly in stromal cells such as tumor-associated fibroblasts and to a minor degree in immune cells such as macrophages and lymphocytes. Likewise, CCL20 expression was primarily detected in tumor-infiltrating immune cells. Thus, investigating the cellular localization of miR-21 and its target CCL20 revealed that both molecules are expressed predominantly in the microenvironment of CRC tumors.

"Mir hei e Verein": Eine Studie über Vereine, Sozialkapital und Wohlstand im Kanton Bern

In diesem Beitrag untersuchen wir den Zusammenhang zwischen dem Sozialkapitalbestand der 382 Gemeinden des Kantons Bern und deren wirtschaftlichen Prosperität. Als Indikator für das Sozialkapital verwenden wir die Anzahl an Vereinen. Nach unseren Recherchen gibt es im Kanton Bern insgesamt 10 130 Vereine. Die statistischen Analysen zeigen, dass selbst unter Kontrolle von weiteren Merkmalen Gemeinden mit vielen Vereinen über ein höheres Einkommen pro Einwohner verfügen. In einer Unterstichprobe von 100 Gemeinden wurde zusätzlich eine schriftliche Befragung von 2 577 Vereinen durchgeführt. Die Resultate ergeben, dass für den Wohlstand der Gemeinden insbesondere die Anzahl an aktiven Mitgliedern ausschlaggebend ist. Vereine mit Fokussierung auf das Gemeinwohl (Putnam-Vereine) haben zudem eine grössere Bedeutung für den Wohlstand als Vereine, die eher Partikularinteressen vertreten (Olson-Vereine). Insgesamt bestätigen die Ergebnisse die Sozialkapitalthese.

Into the abyss of Lake Geneva: the elemo interdisciplinary field investigation using the MIR submersibles

In summer 2011, the two Russian MIR sub- mersibles were brought to Switzerland to perform deep water dives in Lake Geneva. Research teams from several environmental science institutes, both national and inter- national, participated in this interdisciplinary effort to investigate the deeper parts of Lake Geneva. Using the MIRs allowed the scientists to see and precisely select the sites where they could extract specific sediment cores and carry out detailed in situ measurements at the sediment– water boundary. One focus site was the surrounding of the outlet of the wastewater treatment plant of the City of Lausanne, which discharges into the Vidy Bay. The investigations concentrated on the pollution of the local sediments, pollution-related ecotoxicological risks, micro- bial activity and spreading and removal of the effluents from the bay to the open waters of the lake. The other focus site was the Rhoˆne River delta and its subaquatic canyons, which formed as a result of the long-term interplay of the deposition of river-borne sediments and flood-triggered canyon erosion events.

Ob Jude oder Christ, saget mir, wer besser ist? : Historisch sozial-politische Betrachtungen

von A. Weinreich

MicroRNA miR-199a-5p regulates smooth muscle cell proliferation and morphology by targeting Wnt2 signaling pathway

MicroRNA miR-199a-5p impairs tight junction formation leading to increased urothelial permeability in bladder pain syndrome. Now using transcriptome analysis in urothelial TEU-2 cells we implicate it in the regulation of cell cycle, cytoskeleton remodeling, TGF and Wnt signaling pathways. MiR-199a-5p is highly expressed in the smooth muscle layer of the bladder and we altered its levels in bladder smooth muscle cells (SMC) to validate the pathway analysis. Inhibition of miR-199a-5p with antimiR increased SMC proliferation, reduced cell size and up-regulated miR-199a-5p targets, including Wnt2. Overexpression of Wnt2 protein or treating SMCs with recombinant Wnt2 closely mimicked the miR-199a-5p inhibition, whereas down-regulation of Wnt2 in antimiR-expressing SMCs with shRNA restored cell phenotype and proliferation rates. Overexpression of miR-199a-5p in the bladder SMCs significantly increased cell size and up-regulated SM22, SM alpha-actin and SM myosin heavy chain mRNA and protein levels. These changes, as well as increased expression of ACTG2, TGFB1I1, and CDKN1A were mediated by up-regulation of smooth muscle-specific transcriptional activator myocardin at mRNA and protein levels. Myocardin-related transcription factor (MRTF-A) downstream targets Id3 and MYL9 were also induced. Up-regulation of myocardin was accompanied by down-regulation of Wnt-dependent inhibitory Kruppel-like transcription factor 4 (KLF4) in miR-199a-5p overexpressing cells. In contrast, KLF4 was induced in antimiR-expressing cells following the activation of Wnt2 signaling, leading to repression of myocardin-dependent genes. MiR-199a-5p plays a critical role in the Wnt2-mediated regulation of proliferative and differentiation processes in the smooth muscle and may behave as a key modulator of smooth muscle hypertrophy, relevant for organ remodeling.

Impact of miR-21, miR-126 and miR-221 as prognostic factors of clear cell renal cell carcinoma with tumor thrombus of the inferior vena cava

Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.