Zhongliu Fangzhi Yanjiu (Aug 2024)

miR-18a-5p Regulates Colorectal Cancer Proliferation and Progression by Targeting RORA

  • Yifeng CHEN,
  • Shuai WANG,
  • Mingming CHAI,
  • Di ZHANG,
  • Chunxia WANG,
  • Lixia ZHAO,
  • Honglai ZHANG,
  • Xiongfei YANG,
  • Weisheng ZHANG,
  • Tao WANG

DOI
https://doi.org/10.3971/j.issn.1000-8578.2024.23.1372
Journal volume & issue
Vol. 51, no. 8
pp. 667 – 677

Abstract

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ObjectiveTo investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α (RORA) in the proliferation and progression of colorectal cancer (CRC) cells. MethodsThe expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR, FISH, and IHC. Cell proliferation capability was detected through EdU and CFSE assay, cell apoptosis by flow cytometry assay, and cell migration and invasion abilities by cell scratch and Transwell invasion assays, respectively. The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay, cell function rescue test, RT-PCR, and Western blot assay. Finally, bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation, invasion, and progression of CRC via regulating RORA. ResultsmiR-18a-5p exhibited a high expression in CRC tissues and cells (P<0.05) and promoted the proliferation, migration, and invasion of CRC cells (P<0.05). In addition, RORA served as the target gene of miR-18a-5p, and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells (P<0.05). The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A. ConclusionThe targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC. The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC, which can be a potential therapeutic target for CRC.

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