Dataset Information

Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.

ABSTRACT: Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR-223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome-wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR-223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR-223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor-suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.

SUBMITTER: Kurozumi A

PROVIDER: S-EPMC4724812 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.

Kurozumi Akira A Goto Yusuke Y Matsushita Ryosuke R Fukumoto Ichiro I Kato Mayuko M Nishikawa Rika R Sakamoto Shinichi S Enokida Hideki H Nakagawa Masayuki M Ichikawa Tomohiko T Seki Naohiko N

Cancer science 20151205 1

Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, mig ...[more]

PMID: 26509963

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Project description:As a member of the integrin family, integrin α3β1 (ITGA3) has been linked to intercellular communication and serves an important role in the signaling among cells and the extracellular matrix. MicroRNA (miR)‑199a‑5p has been demonstrated to be related to the pathogenesis and progression of multiple malignant diseases. However, the biological functions of miR‑199a‑5p and ITGA3 in colorectal cancer (CRC) have rarely been reported. The aim of the present study was to explore the roles of miR‑199a‑5p and ITGA3 in CRC. Immunohistochemistry staining and western blotting were applied to detect the protein expression of ITGA3 in CRC tissues and cells. Reverse transcription‑quantitative PCR was performed to investigate the expression of miR‑199a‑5p and ITGA3 mRNA. HCT‑116 cells were transfected with miR‑199a‑5p mimics, mimics control, short hairpin RNA targeting ITGA3, or pcDNA‑ITGA3 for the functional experiments. Dual luciferase reporter assay was applied to confirm whether miR‑199a‑5p targeted the 3' untranslated region (3'UTR) of ITGA3. The MTT, Transwell and wound healing assays were used to evaluate the proliferation, invasion and migration of CRC cells. Immunofluorescence assay was used to monitor the epithelial‑mesenchymal transition (EMT) biomarker expression. The results demonstrated downregulation of miR‑199a‑5p and upregulation of ITGA3 in CRC tissues and cell lines. miR‑199a‑5p mimics and knockdown of ITGA3 suppressed the proliferation, invasion and migration of CRC cells. Bioinformatics analysis and luciferase reporter assay indicated that miR‑199a‑5p targeted the 3'UTR of the ITGA3 transcript, and overexpression of ITGA3 reversed the tumor‑suppressive effects of miR‑199a‑5p elevation. In addition, the immunofluorescence assay suggested that miR‑199a‑5p mimics suppressed the EMT of CRC cells, whereas the overexpression of ITGA3 restored this effect. In conclusion, miR‑199a‑5p may act as a tumor suppressor by targeting and negatively regulating ITGA3 in CRC.

Dataset Information

Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.

Publications

Tumor-suppressive microRNA-223 inhibits cancer cell migration and invasion by targeting ITGA3/ITGB1 signaling in prostate cancer.

Similar Datasets

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