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Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.

ABSTRACT: The aberrant expression of microRNAs (miRNAs) is associated with colorectal carcinogenesis, but the underlying mechanisms are not clear. This study showed that the miRNA-27a (miR-27a) was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages-miR-27a was lower at stages III/IV than that at stage II. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected. SGPP1 and Smad2 at mRNA and protein levels were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. Increased miR-27a significantly repressed SGPP1 and Smad2 at transcriptional and translational levels. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Taken together, this study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer. Therefore, miR-27a could be a useful biomarker for monitoring colorectal cancer development and progression, and also could have a therapeutic potential by targeting SGPP1, Smad2 and STAT3 for colorectal cancer therapy.

SUBMITTER: Bao Y

PROVIDER: S-EPMC4148394 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.

Bao Yonghua Y Chen Zhiguo Z Guo Yongchen Y Feng Yansheng Y Li Zexin Z Han Wenliang W Wang Jianguo J Zhao Weixing W Jiao Yunjuan Y Li Kai K Wang Qian Q Wang Jiaqi J Zhang Huijuan H Wang Liang L Yang Wancai W

PloS one 20140828 8

The aberrant expression of microRNAs (miRNAs) is associated with colorectal carcinogenesis, but the underlying mechanisms are not clear. This study showed that the miRNA-27a (miR-27a) was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages-miR-27a was lower at stages III/IV than that at stage II. Bioinformatic and systemic biological analysis pre ...[more]

PMID: 25166914

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Project description:Background:Sustained proliferation and active metastasis are hallmarks of cancer, and they pose major challenges to the development of treatments and a cure for hepatocellular carcinoma (HCC). Thus, the mechanisms of proliferation, migration, and invasion of cancer cells need to be investigated. Many studies indicate that dysregulation of microRNA plays important roles in the progression of HCC, but the role of placenta-specific microRNA (miR-512-3p) in HCC has not been systematically investigated. Purpose:In the current study, the expression, biological function, and mechanisms of miR-512-3p involvement in HCC were investigated. Methods:Real-time quantitative polymerase chain reaction assays were conducted to determine miR-512-3p levels in HCC tissues and cell lines. The StarBase V3.0 online platform was used to compare miR-512-3p levels in HCC tissues with TCGA data and to identify potential miR-512-3p target genes. Associations between miR-512-3p and clinicopathological characteristics were analyzed statistically. MTT, ethynyl deoxyuridine, and transwell assays were performed to assess cell viability, proliferation, migration, and invasion. The luciferase reporter gene assay was used to verify target genes. Recuse assays were performed to confirm whether large tumor suppressor kinase 2 (LATS2) participated in the regulatory effects of miR-512-3p on HCC cell proliferation and motility, and whether miR-512-3p mediated the tumor-promoting effects of hypoxia. Results:miR-512-3p was upregulated in HCC and it was associated with worse survival and unfavorable clinicopathological characteristics. Functional assays indicated that miR-512-3p contributed to HCC cell proliferation, migration, and invasion. Mechanistically, LATS2-a downstream target of miR-512-3p-mediated the tumor-promoting effects of miR-512-3p in HCC. Hypoxia could elevate miR-512-3p levels in HCC cells, and miR-512-3p partially mediated the tumor-promoting effects of hypoxia. Conclusion:Hypoxia-induced miR-512-3p contributes to HCC cell proliferation, migration, and invasion by targeting LATS2 and inhibiting the Hippo/yes-associated protein 1 pathways.

Dataset Information

Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.

Publications

Tumor suppressor microRNA-27a in colorectal carcinogenesis and progression by targeting SGPP1 and Smad2.

Similar Datasets

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