miR-655 Is an EMT-Suppressive MicroRNA Targeting ZEB1 and TGFBR2

Harazono, Yosuke; Muramatsu, Tomoki; Endo, Hironori; Uzawa, Narikazu; Kawano, Tatsuyuki; Harada, Kiyoshi; Inazawa, Johji; Kozaki, Ken Ichi

doi:10.1371/journal.pone.0062757

Cited by 104 publications

(92 citation statements)

References 51 publications

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“…The TargetScan database predicted Zeb-1 and TGFBR2 (type receptor of TGF-b) as the target of miR-655, and the direct link between them was validated by 3 0 -UTR assay. Consistently, overexpression of exogenous miR-655 could inhibit TGF-b-induced EMT by suppression of Zeb-1 and TGFBR2 expression in the PDAC cell line KP1N [50].…”

Section: Microrna and Emtmentioning

confidence: 56%

“…miR-655 was shown to be EMT-suppressive miR by a cell-based reporter system employing a stable clone derived from Panc-1 transfected with a reporter construct containing a promoter sequence of E-cadherin in the 5 0 upstream region of the ZsGreen1 reporter gene [50]. The ratio of fluorescence intensity of ZsGreen1 was measured using 470 synthetic double-strand RNAs mimicking human mature miRNAs, and miR-655 was identified as a novel EMT-suppressive miR in PDAC cells.…”

Section: Microrna and Emtmentioning

confidence: 99%

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Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma

2014

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Pancreatic ductal adenocarcinoma (PDAC) is an intractable disease as a result of its rapid dissemination and resistance to conventional chemotherapy and radiotherapy. Surgical resection is the only curative therapy, but most of the tumors are unresectable at the time of diagnosis. The molecular mechanisms underlying the biological aggressiveness of this tumor type remain to be clarified. Epithelial to mesenchymal transition (EMT) is a developmental process that leads the phenotype shift from an epithelial morphology to a motile, fibroblast-like morphology. Recent studies showed that EMT is involved in the invasion and metastasis of many types of carcinomas including PDAC. In addition, PDAC cells with the EMT phenotype also exhibit chemoresistance and the cancer stem cell property. Various factors such as cytokines, growth factors, or transcriptional factors were found to promote the EMT program in PDAC cells. In this review, we summarize the current knowledge about the EMT in PDAC cells, focusing on the involvement of this process and its regulatory molecules including microRNA during the development of PDAC cells.

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Section: Microrna and Emtmentioning

confidence: 56%

Section: Microrna and Emtmentioning

confidence: 99%

Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma

2014

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“…Reduced expression or loss of the TGFβ type I and type II receptors (TGFBR1 and TGFBR2) has been reported in various types of cancer, including HCC (23)(24)(25). TGFBR2 has been identified as the direct target of numerous miRNAs, including miR-655, miR-520c, miR-373 and miR-211 (26). The results of the present study suggest that TGFBR2 is a novel target of miR-302d in HCC and may partially explain the mechanism by which miR-302d functions in HCC, and why TGFBR2 expression is reduced in HCC.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion

Chen

Guo

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality in China and the third leading cause worldwide. A number of microRNAs (miRNAs) have been implicated in cell cycle progression, growth, apoptosis, angiogenesis and metastasis in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect the levels of miR-302d expression in the tissues of 30 patients with HCC. Cell cycle, growth, apoptosis and migration were analyzed using a cell counting kit, flow cytometry and a Transwell migration assay. Dual-luciferase reporter assays and western blotting were also used to analyze the expression levels of transforming growth factor beta type II receptor (TGFBR2) in HCC cells. The present study evaluated the role of miR-302d in the development and progression of HCC. Abnormally high expression of miR-302d was observed in 80% of HCC specimens. Moreover, patients with lower levels of miR-302d expression experienced a longer survival time than those with higher levels of miR-302d expression. It was demonstrated that miR-302d promoted HCC cell growth and migration, suppressed cell apoptosis and affected cell cycle distribution in vitro, and augmented tumorigenicity in vivo. Furthermore, TGFBR2, which is a tumor suppressor, was confirmed as a target of miR-302d in HCC cells. Dual-luciferase reporter assays indicated that TGFBR2 expression was negatively regulated by miR-302d. Taken together, the results of the present study suggest that miR-302d may serve as a valuable tool for predicting the prognosis of patients with HCC.

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“…reported that miRNAs promote invasion and metastasis through mediating EMT (18). In order to evaluate the function of miR-106b in inducing EMT in ESCC, we examined the mRNA and protein expression of the epithelial marker E-cadherin and the mesenchymal marker vimentin in EC-1 cells.…”

Section: Downregulation Of Mir-106b Expression Could Inhibit the Indumentioning

confidence: 99%

miR-106b promotes cell invasion and metastasis via PTEN mediated EMT in ESCC

et al. 2018

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Abstract. MicroRNA (miR)-106b serves an essential function in a variety of human cancer types, particularly in the process of invasion and metastasis. However, the function and mechanism of miR-106b in the invasion and metastasis of esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, it was demonstrated that miR-106b was upregulated in ESCC tissues and cell lines. Furthermore, miR-106b expression in ESCC tissues was positively associated with lymphatic metastasis. Inhibition of miR-106b in EC-1 and EC9706 cells decreased not only the invasion and metastasis ability but also the proliferation ability of EC-1 and EC9706 cells. In addition, miR-106b had the ability to induce epithelial-to-mesenchymal transition (EMT) in EC-1 and EC9706 cells. In terms of the underlying mechanism, it was revealed that miR-106b promoted the invasion, metastasis and proliferation ability of EC-1 and EC9706 cells by directly targeting phosphatase and tension homolog (PTEN). Furthermore, miR-106b induced EMT in EC-1 and EC9706 cells by suppressing the expression of PTEN. In summary, the present study revealed that miR-106b contributed to invasion and metastasis in ESCC by regulating PTEN mediated EMT. Downregulation of miR-106b may be a novel strategy for preventing tumor invasion and metastasis. IntroductionEsophageal squamous cell carcinoma (ESCC) is the most malignant lesion in China, particularly in Linzhou, Henan (1).Treatment of ESCC is largely useless due to the occurrence of invasion and metastasis in the early stage. However, the mechanism of invasion and metastasis of ESCC has been poorly elucidated (2).Epithelial-to-mesenchymal transition (EMT) now is always viewed as a key event that occurs during cancer invasion and metastasis. However, current understanding of the alterations that give rise to the occurrence of EMT is limited. MicroRNAs (miRNA/miRs) are small non-coding RNA molecules that may directly regulate target gene expression by binding to their 3'-untranslated regions (3'-UTRs) (3,4). Furthermore, miRNAs have been demonstrated to serve notable functions in tumor invasion and metastasis by functioning as EMT suppressors or inducers (5,6). miR-106b is a type of miRNA transcribed from the miR-106b-25 cluster located on chromosome 7 (7). Yau et al (8) reported that miR-106b overexpressed in hepatocellular carcinoma cells and that the overexpression of miR-106b may promote cell migration and metastasis by activating the EMT process. Zhou et al (9) additionally demonstrated that miR-106b contributed as an EMT inducer in breast cancer. However, whether miR-106b participates in the invasion and metastasis process of ESCC by inducing EMT and the mechanism of how miR-106b induces EMT in ESCC had not been fully explored until now. miRNAs participate in the occurrence and development of a cancer by regulating the post-transcriptional process of their target gene. Several genes have been verified to be the targets of miR-106b, including transforming growth factor-β type II receptor, cyclin de...

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miR-655 Is an EMT-Suppressive MicroRNA Targeting ZEB1 and TGFBR2

Cited by 104 publications

References 51 publications

Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma

Involvement of epithelial to mesenchymal transition in the development of pancreatic ductal adenocarcinoma

MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion

miR-106b promotes cell invasion and metastasis via PTEN mediated EMT in ESCC

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