MicroRNA Expression in Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus: Associations with Survival

Mathé, Ewy A.; Nguyen, Giang Huong; Bowman, Elise D.; Zhao, Yiqiang; Budhu, Anuradha; Schetter, Aaron J.; Braun, Rosemary; Reimers, Mark; Kumamoto, Kensuke; Hughes, Duncan B.; Altorki, Nasser K.; Casson, Alan G.; Liu, Chang–Gong; Wang, Xin Wei; Yanaihara, Nozomu; Hagiwara, Nobutoshi; Dannenberg, Andrew J.; Miyashita, Masao; Croce, Carlo M.; Harris, Curtis C.

doi:10.1158/1078-0432.ccr-09-1467

Cited by 347 publications

(309 citation statements)

References 49 publications

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…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: 80%

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

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 80%

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

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Compared with NEST, a significant down-regulation of miR-210 expression was noted in ESCC. On the other hand, the expression of miR-31, which has been reported to be not altered between ESCC and NEST (16,17), showed no significant difference (Fig. 1B).…”

Section: Mir-210 Expression Is Significantly Down-regulated In Escc mentioning

confidence: 77%

MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1)

Tsuchiya

Fujiwara

Sato

et al. 2011

Journal of Biological Chemistry

177

155

View full text Add to dashboard Cite

The importance of microRNAs (miRNAs) in human malignancies has been well recognized. Here, we report that the expression of microRNA-210 (miR-210) is down-regulated in human esophageal squamous cell carcinoma and derived cell lines. Marked decreases in the level of miR-210 were observed especially in poorly differentiated carcinomas. We found that miR-210 inhibits cancer cell survival and proliferation by inducing cell death and cell cycle arrest in G 1 /G 0 and G 2 /M. Finally, we identified fibroblast growth factor receptor-like 1 (FGFRL1) as a target of miR-210 in esophageal squamous cell carcinoma and demonstrated that FGFRL1 accelerates cancer cell proliferation by preventing cell cycle arrest in G 1 /G 0 . Taken together, our findings show an important role for miR-210 as a tumor-suppressive microRNA with effects on cancer cell proliferation. MicroRNAs (miRNAs)2 are evolutionarily conserved small noncoding RNAs (20 -23 nucleotides) that bind to complementary sequences in the 3Ј-untranslated region (UTR) of target messenger RNAs (mRNAs) and regulate gene expression by the cleavage of target mRNAs and/or translational inhibition (1). Currently, Ͼ800 human miRNAs have been identified and registered in the miRNA database, miRBase (2). miRNAs play important roles in the differentiation of various cell types and in the initiation and progression of cancer, and it has been shown that the expression of some miRNAs is altered during cell differentiation and in malignancies (1, 3, 4).In a recent study, we identified microRNA-210 (miR-210) as one of the miRNAs that is markedly differentially expressed during the process of epithelial differentiation (3). It has been reported that miR-210 expression is down-regulated during epithelial-mesenchymal transition, the aberrant activation of which triggers cancer pathology (5). Carcinomas are derived from epithelial cells, and poor prognosis in patients with carcinoma is associated with the disruption of characteristics of differentiated epithelial cells, such as cell junctions and polarity (6 -8). Hence, given that the expression of miR-210 appears to be correlated well with epithelial differentiation, miR-210 might play a suppressive role in carcinomas. In support of this idea, allelic deletions at the miR-210 locus have been observed in 64% of cases of ovarian cancer (9), and ectopic expression of miR-210 represses tumor growth when human cancer cell lines are implanted into immunodeficient mice (10). However, the clinical roles of miR-210 in carcinomas and the mechanisms by which it represses tumor growth remain unknown.In this study, we investigated the functional role of miR-210 in the growth of carcinomas and the mechanism by which it acts using clinical samples as well as cell lines of esophageal squamous cell carcinoma (ESCC). ESCC is a highly aggressive malignancy with a 5-year survival rate of 10% worldwide. It has been used as a model to study the mechanisms of dysregulated epithelial differentiation and epithelial-mesenchymal transition in carcinomas (11, 12). E...

show abstract

“…Until very recently, miR-375 has been found to be deregulated in some malignancies, including live tumor with β-catenin mutation, head and neck squamous cell carcinoma and pancreatic adenocarcinomas [26][27][28][29], whereas little is known about the molecular targets of miR-375 in these cancer. To our knowledge, JAK2 may be the first identified target gene that is involved in the regulation of carcinogenesis by miR-375.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

View full text Add to dashboard Cite

MicroRNA Expression in Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus: Associations with Survival

Cited by 347 publications

References 49 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

MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1)

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

Contact Info

Product

Resources

About