miR-30 Family: A Promising Regulator in Development and Disease

Mao, Ling; Liu, Shiming; Hu, Lin; Li, Jia; Wang, Hairong; Guo, Ming; Chen, Chao; Liu, Yun; Xu, Lin

doi:10.1155/2018/9623412

Cited by 110 publications

(100 citation statements)

References 52 publications

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“…The miR-30-family is located on three chromosomal regions (chromosome 1: miR-30c-1 and miR-30e; chromosome 6: miR-30c-2 and miR-30a; chromosome 8: miR-30b and miR-30d) and consists of 12 different mature miRNAs [ 25 ]. The seed sequences of the guide strands of the miR-30 family are identical ( GUAAACA ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tanaka

Okada

Hozaka

et al. 2020

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA (miRNA) signature analysis of PDAC revealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC.

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Section: Introductionmentioning

confidence: 99%

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tanaka

Okada

Hozaka

et al. 2020

Cancers

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“…MiRNA-21 partially promotes hepatic lipid accumulation and cancer progression by interacting with the Hbp1-p53-Srebp1c pathway, miRNA-21 also regulates triglyceride and cholesterol metabolism by targeting HMGCR in NAFLD [24,25]. Recent studies have found that the miR-30 family play an important role in adipocyte differentiation and fat synthesis [26]. A Spanish study conducted by Latorre et al showed that patients with NAFLD and obesity had lower miR-30b-5p level in the liver compared with simple obese patients, and the expression of miR-30b-5p was decreased in hepatocytes after stimulated with fatty acid in vitro [27].…”

Section: Introductionmentioning

confidence: 99%

MiR-30b-5p regulates the lipid metabolism by targeting PPARGC1A in Huh-7 cell line

Zhang

Dong

et al. 2020

Lipids Health Dis

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Background: MiRNAs are a group of multifunctional non-coding RNAs which play an important role in the various physiological processes including the development of NAFLD. Recent studies have shown that miR-30b-5p tightly associated with the abnormal lipid metabolism in patients with NAFLD, but the detailed mechanism of miR-30b-5p in the lipid metabolism was remain unclear. The aim of this study was to investigate the effect of miR-30b-5p on the lipid metabolism in hepatocellular carcinoma Huh-7 cells. Material and methods: The correlation of intracellular fat content with the expression of miR-30b-5p in Huh-7 cells and HepG2 cells was investigated by treated cells with different concentrations of FFAs. The effect of miR-30b-5p on the lipid deposition in Huh-7 cells was tested by oil red O staining and TG concentrations measurement. qRT-PCR and western blot were used to investigate the lipid metabolism-related genes PPAR-α, SREBP-1, and GULT1 in miR-30b-5p overexpressed or inhibited Huh-7 cells. Target genes of miR-30b-5p were predicted using starBase, miRDB, and TargetScan databases and verified by qRT-PCR and western blot. Results: The expression of miR-30b-5p was significant decreased in the FFAs treated Huh-7 cells and HepG2 cells. Overexpressing miR-30b-5p in Huh-7 cells decreased the number and size of lipid droplets and intracellular TG concentrations in Huh-7 cells. Expression of fatty acid oxidation related gene PPAR-α was increased and expression of lipid synthesis related gene SREBP-1 was decreased in the miR-30b-5p overexpressed Huh-7 cells. In addition, miR-30b-5p regulates the intracellular lipid metabolism by targeting PPARGC1A. Conclusions: Overexpression of miR-30b-5p could reduce the intracellular fat deposition in Huh-7 cells, and miR-30b-5p might regulate the intracellular lipid metabolism by targeting the PPARGC1A in Huh-7 cells.

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“…miR-30 family miRNAs are tumor suppressors frequently found to be downregulated in multiple types of cancers including the cancers of lung (Kumarswamy et al, 2012;Yang et al, 2017;Mao et al, 2018). Our findings suggest that a large number of Cd-upregulated genes were targets of miR-30 family (Fig.…”

Section: Exposure Induces Snail Expressionmentioning

confidence: 62%

Cadmium exposure upregulates SNAIL through miR-30 repression in human lung epithelial cells

Tanwar

Zhang

Jagannathan

et al. 2019

Toxicology and Applied Pharmacology

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Cadmium (Cd) is a known human lung carcinogen. In addition, Cd exposure is associated with several lung diseases including emphysema, chronic obstructive pulmonary disease (COPD), asthma and fibrosis. Although earlier studies have identified several processes dysregulated by Cd exposure, the underlying mechanisms remain unclear. Here, we examined the transcriptome of lung epithelial cells exposed to Cd to understand the molecular basis of Cd-induced diseases. Computational analysis of the transcriptome predicted a significant number of Cd-upregulated genes to be targets of miR-30 family miRNAs. Experimental validation showed downregulation of all the miR-30 family members in Cd exposed cells. We found SNAIL, an EMT master regulator, to be the most upregulated among the miR-30 targets. Furthermore, we found decrease in the levels of epithelial marker E-cadherin (CDH1) and increase in the levels of mesenchymal markers, ZEB1 and vimentin. This suggested induction of EMT in Cd exposed cells. Luciferase reporter assays showed that miR-30 repressed SNAIL by directly targeting its 3′ UTR. Over expression of miR-30e and miR-30e mimics reduced Cd-induced SNAIL upregulation. Our results suggest that miR-30 negatively regulates SNAIL in lung epithelial cells and that Cd-induced downregulation of miR-30 relieves this repression, resulting in SNAIL upregulation and EMT induction. EMT plays a major role in many diseases associated with Cd exposure including fibrosis, COPD and cancer and metastasis. Therefore, our identification of miR-30 downregulation in Cd exposed cells and the consequent activation of SNAIL provides important mechanistic insights into lung diseases associated with Cd exposure.

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miR-30 Family: A Promising Regulator in Development and Disease

Cited by 110 publications

References 52 publications

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

MiR-30b-5p regulates the lipid metabolism by targeting PPARGC1A in Huh-7 cell line

Cadmium exposure upregulates SNAIL through miR-30 repression in human lung epithelial cells

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