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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.
AuthorsTing-Ting Lu, Xia Tao, Hua-Lei Li, Ling Gai, Hua Huang, Feng Li
JournalAsian journal of andrology (Asian J Androl) 2022 Nov-Dec Vol. 24 Issue 6 Pg. 643-652 ISSN: 1745-7262 [Electronic] China
PMID35295003 (Publication Type: Journal Article)
Chemical References
  • GAS5 long non-coding RNA, human
  • MicroRNAs
  • MIRN18A microRNA, human
  • Paclitaxel
  • Protein Serine-Threonine Kinases
  • RNA, Long Noncoding
  • STK4 protein, human
Topics
  • Humans
  • Male
  • Cell Line, Tumor
  • Cell Proliferation (genetics)
  • Gene Expression Regulation, Neoplastic
  • MicroRNAs (genetics, metabolism)
  • Neoplastic Stem Cells
  • Paclitaxel (pharmacology, therapeutic use)
  • Prostatic Neoplasms (drug therapy, genetics)
  • Protein Serine-Threonine Kinases (genetics, metabolism)
  • RNA, Long Noncoding (genetics, metabolism)
  • Epithelial-Mesenchymal Transition

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