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LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.

ABSTRACT: The onset of prostate cancer (PCa) is often hidden, and recurrence and metastasis are more likely to occur due to chemotherapy resistance. Herein, we identified downregulated long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in PCa that was associated with metastasis and paclitaxel resistance. GAS5 acted as a tumor suppressor in suppressing the proliferation and metastasis of paclitaxel-resistant PCa cells. GAS5 overexpression in vivo inhibited the tumor growth of xenografts and elevated PCa sensitivity to paclitaxel. Combination of GAS5 and paclitaxel treatment showed great potential in PCa treatment. Moreover, mechanistic analysis revealed a novel regulatory network of GAS5/miR-18a-5p/serine/threonine kinase 4 (STK4) that inhibits epithelial-to-mesenchymal transition (EMT) and enhances tumor stem cell-like-mediated sensitivity to paclitaxel in PCa. These findings provide a novel direction for the development of a potential adjunct to cancer chemotherapy that aims to improve the sensitivity of chemotherapy drugs in PCa.

SUBMITTER: Lu TT

PROVIDER: S-EPMC9809493 | biostudies-literature | 2022 Nov-Dec

REPOSITORIES: biostudies-literature

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LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.

Lu Ting-Ting TT Tao Xia X Li Hua-Lei HL Gai Ling L Huang Hua H Li Feng F

Asian journal of andrology 20221101 6

The onset of prostate cancer (PCa) is often hidden, and recurrence and metastasis are more likely to occur due to chemotherapy resistance. Herein, we identified downregulated long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in PCa that was associated with metastasis and paclitaxel resistance. GAS5 acted as a tumor suppressor in suppressing the proliferation and metastasis of paclitaxel-resistant PCa cells. GAS5 overexpression in vivo inhibited the tumor growth of xenografts and elevat ...[more]

PMID: 35295003

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Project description:OBJECTIVE:To investigate the role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA-GAS5) in breast cancer progression and epithelial-mesenchymal transition (EMT) of the cancer cells. METHODS:Real-time quantitative PCR (qRT-PCR) was used to detect the expression of lncRNA-GAS5 in 37 pairs of breast cancer and adjacent non-tumor tissues and in parental MCF-7 cells and paclitaxel-resistant MCF-7 (MCF-7/PR) cells, and the correlation of lncRNA-GAS5 expression with the clinical stage and lymph node metastasis of breast cancer was investigated. The expressions of the genes related with cell cycle and EMT at both the mRNA and protein levels were detected using qRT-PCR, Western blotting and immunohistochemistry. The changes in the biological behaviors and morphology of breast cancer cells with either lncRNA-GAS5 knockdown or overexpression were observed. Nude mouse models were established bearing breast cancer xenografts derived from MCF-7/PR cells or MCF-7/PR cells over-expressing lncRNA-GAS5, and the inhibitory effect of paclitaxel on tumor growth was evaluated. RESULTS:The transcriptional levels of lncRNA-GAS5 were significantly lower in breast cancer tissues than in the adjacent non-tumor tissues (P<0.05), and decreased lncRNA-GAS5 expression was significantly correlated with TNM stage and lymph node metastasis of breast cancer (P<0.05). lncRNA-GAS5 expression was also significantly lowered in paclitaxel-resistant breast cancer cells and showed a positive correlation with P21 expression and a negative correlation with CDK6. MCF-7 cells during EMT presented with a lowered expression of lncRNA-GAS5, whereas lncRNA-GAS5 over-expression strongly suppressed MCF-7/PR cell migration and invasion, and increased the susceptibility of the cells to paclitaxel. In the tumor-bearing nude mouse models, lncRNA-GAS5 overexpression in the tumor cells obviously enhanced the inhibitory effect of paclitaxel on tumor growth and lung metastasis by reversing the EMT marker proteins. CONCLUSION:A decreased expression of lncRNA-GAS5 promotes lung metastasis of breast cancer by inducing EMT, suggesting the potential of lncRNA-GAS5 as a therapeutic target in breast cancer.

Dataset Information

LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.

Publications

LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer.

Similar Datasets

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