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

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

VernacularTitle:miR-18a-5p靶向调控RORA在结直肠癌增殖进展中的作用及临床意义
Author: Yifeng CHEN ^{1
,

2} ; Shuai WANG ^{1
,

2} ; Mingming CHAI ^{1
,

2} ; Di ZHANG ^{1
,

3
,

4} ; Chunxia WANG ^{1
,

3
,

4} ; Lixia ZHAO ^{1
,

3
,

4} ; Honglai ZHANG ^{1
,

2} ; Xiongfei YANG ^{1
,

2} ; Weisheng ZHANG ^{1
,

2} ; Tao WANG ^{1
,

2}
Author Information

1. NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, China
2. Department of Anorectal Surgery, Gansu Provincial Hospital, Lanzhou 730000, China.
3. Department of Anorectal Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
4. The First Clinical Medical College of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China.
Publication Type:BASICRESEARCH
Keywords: miR-18a-5p; RORA; Colorectal cancer; Proliferation
From: Cancer Research on Prevention and Treatment 2024;51(8):667-677
CountryChina
Language:Chinese
Abstract: Objective To 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. Methods The 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. Results miR-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. Conclusion The 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.