MicroRNA-30a-3p inhibits tumor proliferation, invasiveness and metastasis and is downregulated in hepatocellular carcinoma

Wang, W.; Lin, Hui; Zhou, Linghui; Zhu, Qianqian; Gao, Shuyang; Xie, Haiyang; Liu, Zhaobo; Xu, Zhifei; Wei, Jianfeng; Huang, Xin; Zheng, Shusen

doi:10.1016/j.ejso.2013.11.008

Cited by 71 publications

(61 citation statements)

References 29 publications

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“…Supporting our observations, almost the entire miR-30 family (miR-30a,b,c,d) was shown to be downregulated in metastatic RCC tissue21. MiR-30a-3p has been proven to have the ability to restore CDH1 expression in hepatocellular carcinoma22. Further, it was observed that hypoxia induces EMT in RCC cells through downregulation of miR-30c-5p, which leads to subsequent increase of Slug expression and repression of E-cadherin production23.…”

Section: Discussionsupporting

confidence: 77%

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

Mlčochová

Macháčková

Rabien

et al. 2016

Sci Rep

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Clear-cell renal cell carcinomas (ccRCCs) are genetically heterogeneous tumors presenting diverse clinical courses. Epithelial-mesenchymal transition (EMT) is a crucial process involved in initiation of metastatic cascade. The aim of our study was to identify an integrated miRNA/mRNA signature associated with metastasis and prognosis in ccRCC through targeted approach based on analysis of miRNAs/mRNAs associated with EMT. A cohort of 230 ccRCC was included in our study and further divided into discovery, training and validation cohorts. EMT markers were evaluated in ccRCC tumor samples, which were grouped accordingly to EMT status. By use of large-scale miRNA/mRNA expression profiling, we identified miRNA/mRNA with significantly different expression in EMT-positive tumors and selected 41 miRNAs/mRNAs for training phase of the study to evaluate their diagnostic and prognostic potential. Fifteen miRNAs/mRNAs were analyzed in the validation phase, where all evaluated miRNA/mRNA candidates were confirmed to be significantly deregulated in tumor tissue. Some of them significantly differed in metastatic tumors, correlated with clinical stage, with Fuhrman grade and with overall survival. Further, we established an EMT-based stage-independent prognostic scoring system enabling identification of ccRCC patients at high-risk of cancer-related death. Finally, we confirmed involvement of miR-429 in EMT regulation in RCC cells in vitro.

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Section: Discussionsupporting

confidence: 77%

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

Mlčochová

Macháčková

Rabien

et al. 2016

Sci Rep

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“…It is likely that additional pathways regulated by miR-30s also contribute to the antitumor effects. Although overexpression of miR-30s in distant organs has no effect on primary tumor growth, interestingly, miR-30s have been reported as tumor suppressors that inhibit proliferation in pancreatic cancer (34), hepatocellular carcinoma (35), breast cancer (36), myeloma (37), and colorectal cancer (17). The miR-30 family is also implicated to inhibit epithelial-mesenchymal transition in prostate cancer cells (38), pancreatic cells (39), and hepatocytes (22).…”

Section: Discussionmentioning

confidence: 99%

The miR-30 Family Inhibits Pulmonary Vascular Hyperpermeability in the Premetastatic Phase by Direct Targeting of Skp2

Jia

et al. 2015

Clinical Cancer Research

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Purpose: Before metastasis, primary tumor can create a premetastatic niche in distant organ to facilitate the dissemination of tumor cells. In the premetastatic phase, the permeability of pulmonary vasculatures is increased to accelerate the extravasation of circulating tumor cells. However, it is not clear whether local miRNAs contribute to the vascular hyperpermeability of the premetastatic niche.Experimental Design: The expression of total miRNAs was determined using microarray in series of premetastatic lungs from tumor-bearing mice. Significantly differentially expressed miRNAs were identified and validated with qRT-PCR. Vascular permeability assays, vascular mimic systems, and orthotopic tumor models were used to investigate roles of selected miRNAs and target genes in premetastatic hyperpermeability.Results: We identified a miRNA signature in premetastatic lungs. Among these miRNAs, miR-30a, b, c, d, and e were significantly attenuated. Subsequent investigations elucidated that lung fibroblast-derived miR-30s stabilized pulmonary vessels. Overexpression of miR-30s in lungs postponed metastasis and extended overall survival of B16 tumor-bearing mice. Following studies uncovered that Skp2 was directly targeted by miR30s. Overexpression of Skp2 could disrupt pulmonary vessels, promote lung metastasis, and decrease overall survival of B16 tumor-bearing mice.Conclusions: These findings illuminate a novel mechanism for the modulation of premetastatic niches by miR-30s, which suggest that miR-30s represent not only promising targets for antimetastasis therapy but also indicators for metastasis.

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“…By directly targeting metadherin (MTDH), miR-30a inhibited liver cancer cell proliferation and promoted apoptosis as a onco-suppressor through PTEN/ AKT pathway [98]. Further study demonstrated that miR-30a regulated HCC cellular proliferation, invasion and metastasis by a mechanism involving reduction of vimentin and MMP3 expression and restoration of E-cadherin expression [70]. …”

Section: Activities Of Mir-30a In Cancer Progressionmentioning

confidence: 99%

“…Levels of miR-30a were found to remarkably descend in most of cancer tissues compared with those in adjacent non-tumorous tissues, such as colorectal cancer [67, 68], hepatocellular carcinoma [69, 70], breast cancer [71], renal cell carcinoma [72], chondrosarcoma [73], ovarian papillary serous carcinoma [74], and anaplastic thyroid cancer [75]. Furthermore, miR-30a expression decreased in patients with shorter overall survival and disease-free survival time in patients with NSCLC [19] and urothelial carcinoma of bladder [76], consistent with the lower expression of miR-30a in tumor tissues compared to their non-tumor lung tissues.…”

Section: Expression and The Clinical Significance Of Mir-30a In Cancermentioning

confidence: 99%

The Versatile Role of microRNA-30a in Human Cancer

Xiang

Chen²,

Chen³

2017

Cell Physiol Biochem

2,602

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MicroRNAs (miRNAs) are a group of noncoding RNA molecules of 20-23 nucleotides length that negatively regulate gene expressions in numerous cellular processes. Through complementary paring with target mRNAs, miRNAs have frequently emerged as dual regulators of cancer development by acting on multiple signaling pathways, thereby act as novel biomarkers for cancer diagnosis, prognosis, and prediction of response to treatment. As one of them, miR-30a has been found to act as an onco-suppressor of tumorigenesis pathways through inhibition of cellular proliferation, migration and invasion. Simultaneously, miR-30a plays a progressing role in several types of cancer, determined by relevant target genes as well. In the present review, we summarize recent research regarding miR-30a, including its biological function, expression and regulation, especially focusing on its role in cancer development and progression. Clinically, miR-30a may serve as a potential target in the diagnosis and therapy of human cancer.

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MicroRNA-30a-3p inhibits tumor proliferation, invasiveness and metastasis and is downregulated in hepatocellular carcinoma

Cited by 71 publications

References 29 publications

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

Epithelial-mesenchymal transition-associated microRNA/mRNA signature is linked to metastasis and prognosis in clear-cell renal cell carcinoma

The miR-30 Family Inhibits Pulmonary Vascular Hyperpermeability in the Premetastatic Phase by Direct Targeting of Skp2

The Versatile Role of microRNA-30a in Human Cancer

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