MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2

Ding, Ling; Xu, Yanjun; Zhang, Wei; Deng, Yujie; Si, Misi; Du, Ying; Yao, Haomi; Liu, Xuyan; Ke, Yuehai; Si, Jianmin; Zhou, Tian

doi:10.1038/cr.2010.79

Cited by 314 publications

(273 citation statements)

References 39 publications

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“…Although several studies did not notice an upregulation of miR-375 in prostate carcinoma samples, various studies observed increased levels of this miRNA in prostate cancer serum samples (44,45). Publications confirm that miR-375 is downregulated in other cancer types such as cervical, lung, or head and neck carcinoma, as well as glioma (46)(47)(48)(49)(50) but upregulated in breast carcinoma (51). Likewise, miR-15a was previously shown to be downregulated in metastasizing prostate carcinoma (18).…”

Section: Discussionmentioning

confidence: 60%

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

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MicroRNAs (miRNA) posttranscriptionally regulate gene expression and are important in tumorigenesis. Previous deep sequencing identified the miRNA profile of prostate carcinoma versus nonmalignant prostate tissue. Here, we generated miRNA expression profiles of prostate carcinoma by deep sequencing, with increasing tumor stage relative to corresponding nonmalignant and healthy prostate tissue, and detected clearly changed miRNA expression patterns. The miRNA profiles of the healthy and nonmalignant tissues were consistent with our previous findings, indicating a high fidelity of the method employed. In the tumors, quantitative real-time PCR (qRT-PCR) analysis of 40 paired samples of prostate carcinoma versus normal tissue revealed significant upregulation of miR-20a, miR-148a, miR-200b, and miR-375 and downregulation of miR-143 and miR-145. Hereby, miR-375 increased from normal to organ-confined tumors (pT2 pN0), slightly decreased in tumors with extracapsular growth (pT3 pN0), but was then expressed again at higher levels in lymph node metastasizing (pN1) tumors. The sequencing data for miR-375 were confirmed by Northern blotting and qRT-PCR. The regulation for other selected miRNAs could, however, not be confirmed by qRT-PCR in individual tumor stages. MiR-200b, in addition to miR-200c and miR-375 reduced the expression of SEC23A. Interestingly, miR-375, found by sequencing in pT2 upregulated by us and others in tumor versus normal tissue, and miR-15a, found by sequencing in pT2 and pT3 and in the metastasizing tumors, target the phosphatases PHLPP1 and PHLPP2, respectively. PHLPP1 and PHLPP2 dephosphorylate members of the AKT family of signal transducers, thereby inhibiting cell growth. Coexpression of miR-15a and miR-375 resulted in downregulation of PHLPP1/2 and strongly increased prostate carcinoma cell growth.Implications: These genomic data reveal relevant miRNAs in prostate cancer that may have biomarker and therapeutic potential. Mol Cancer Res; 12(2); 250-63. Ó2013 AACR. IntroductionProstate carcinoma is the second most frequently diagnosed malignancy and a leading cause of cancer-related death in men worldwide (1). The underlying mechanisms resulting in invasive growth after dissemination of the primary tumor from the initial site in the prostate are not completely understood. MicroRNAs (miRNAs) are now recognized as contributing factors to the induction, growth, and metastasis

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Section: Discussionmentioning

confidence: 60%

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

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“…Altogether, these results suggest that some miRNAs may be under direct beta-catenin/TCF4 control with others being regulated by downstream effectors and/or depend on simultaneous inputs from additional factors (Labbe et al, 2007). dnTCF4-responsive miRNAs are downregulated in CRC specimens and CRC cell lines Among the numerous miRNAs altered as a consequence of dnTCF4 overexpression, we noticed several of the upregulated miRNAs to have been previously associated with restriction of cancer cell growth (miR449a, (Henson et al, 2009;Noonan et al, 2009;Slaby et al, 2009;Chen et al, 2010;Ding et al, 2010;Ostenfeld et al, 2010). Interestingly, in addition to prominent growth-inhibitory miRNAs commonly downregulated in CRC, such as miR-126 and miR-145 (Guo et al, 2008;Schepeler et al, 2008), several miRNAs with unknown function in CRC cells (for example, miR-574-3p, miR-30e-3p and miR-139-5p) were also upregulated, which prompted us to hypothesize that some of these miRNAs may also be dysregulated in CRC.…”

Section: Resultsmentioning

confidence: 81%

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

et al. 2011

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“…Inhibition of miR-375 in ERa-positive MCF-7 cells reduced both ERa activation and cell proliferation [35]. In gastric cancer, miRNA-375 was found to be the most down-regulated miRNA, and ectopic expression of miRNA-375 in gastric carcinoma cells markedly reduced cell viability by a mechanism involving the caspase-mediated apoptosis pathway [37]. Interestingly, the authors reported that expression of miR-375 inhibited expression of PDK1, a direct target of miR-375, and resulted in the suppression of Akt phosphorylation [36].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of microRNA‐375 and its role in melanoma development in humans

et al. 2011

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Edited by Tamas Dalmay Keywords:Epigenetic regulation MicroRNA miR-375 Cell invasion Human melanoma a b s t r a c tTo identify epigenetically regulated miRNAs in melanoma, we treated a stage 3 melanoma cell line WM1552C, with 5AzadC and/or 4-PBA. Several hypermethylated miRNAs were detected, one of which, miR-375, was highly methylated and was studied further. Minimal CpG island methylation was observed in melanocytes, keratinocytes, normal skin, and nevus but hypermethylation was observed in patient tissue samples from primary, regional, distant, and nodular metastatic melanoma. Ectopic expression of miR-375 inhibited melanoma cell proliferation, invasion, and cell motility, and induced cell shape changes, strongly suggesting that miR-375 may have an important function in the development and progression of human melanomas.

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MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2

Cited by 314 publications

References 39 publications

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Attenuation of the beta-catenin/TCF4 complex in colorectal cancer cells induces several growth-suppressive microRNAs that target cancer promoting genes

Epigenetic regulation of microRNA‐375 and its role in melanoma development in humans

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