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Volume 24, Issue 6 (November 2022) 24, 643–652; 10.4103/aja2021117
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
Ting-Ting Lu1,2, Xia Tao3, Hua-Lei Li4, Ling Gai5, Hua Huang6, Feng Li1
1 Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
2 Department of Pathology, Nantong University Medical School, Nantong 226001, China
3 Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong 226001, China
4 Department of Urology, Affiliated Hospital of Nantong University, Nantong 226001, China
5 Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong 226001, China
6 Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, China
Correspondence: Dr. F Li (lifeng@ntu.edu.cn)
Date of Submission 08-Jul-2021 Date of Acceptance 12-Dec-2021 Date of Web Publication 15-Mar-2022
| Abstract |
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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.
Keywords: epithelial-to-mesenchymal transition; growth arrest-specific 5; long noncoding RNA; paclitaxel; prostate cancer
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