LncRNA SNHG4 promotes malignant biological behaviors and immune escape of colorectal cancer cells by regulating the miR-144-3p/MET axis

Ning Zhou; Ying Chen; Li Yang; Tingting Xu; Fanrong Wang; Liqiao Chen; Jun Liu; Guangguo Liu

LncRNA SNHG4 promotes malignant biological behaviors and immune escape of colorectal cancer cells by regulating the miR-144-3p/MET axis

Am J Transl Res. 2021 Oct 15;13(10):11144-11161. eCollection 2021.

Authors

Ning Zhou¹, Ying Chen², Li Yang³, Tingting Xu¹, Fanrong Wang¹, Liqiao Chen¹, Jun Liu⁴, Guangguo Liu⁵

Affiliations

¹ Department of Pathology, Sichuan Mianyang 404 Hospital Mianyang 621000, Sichuan Province, China.
² Department of Pathology, Guiqian International General Hospital Guiyang 550000, Guizhou Province, China.
³ Department of Pathology, The People's Hospital of Santai County Mianyang 621000, Sichuan Province, China.
⁴ Department of General Surgery, Sichuan Mianyang 404 Hospital Mianyang 621000, Sichuan Province, China.
⁵ Department of Oncology, Sichuan Mianyang 404 Hospital Mianyang 621000, Sichuan Province, China.

PMID: 34786048
PMCID: PMC8581836

Abstract

Objective: This study aimed to explore the underlying mechanism of long noncoding RNA (lncRNA) SNHG4 regulating MET to participate in the malignant biologic behaviors and immune escape of colorectal cancer (CRC) by sponging miR-144-3p.

Methods: CRC tissues were collected and the expression levels of lncRNA SNHG4, miR-144-3p, and MET were detected by quantitative real-time PCR (qRT-PCR). Then, the localization of lncRNA SNHG4 was studied by fluorescence in situ hybridization (FISH), and the regulatory relationship among lncRNA SNHG4, miR-144-3p, and MET was verified by dual-luciferase reporter assay. Next, cell counting kit-8 (CCK-8), Clone formation assay, and Transwell migration assay were carried out to evaluate cell proliferation, colony formation, and invasion, respectively. Flow cytometry was performed to evaluate cell apoptosis. Western blotting was applied to semi-quantify the expression levels of MET and PD-L1 in cells.

Results: LncRNA SNHG4 expression was upregulated in CRC tissues. Knockdown of lncRNA SNHG4 suppressed the proliferation, colony formation and invasion of CRC cells (all P<0.05). LncRNA SNHG4 directly regulated miR-144-3p, by which either lncRNA SNHG4 knockdown or miR-144-3p overexpression can inhibit CD4+ T cell apoptosis (both P<0.05) to suppress immune escape. Either overexpression of lncRNA SNHG4 or knockdown of miR-144-3p activated PD-1/PD-L1 and induced CD4+ T cell apoptosis (both P<0.05). LncRNA SNHG4 targeted and regulated MET through the regulation of miR-144-3p, while overexpression of MET can partially reverse the effect of lncRNA SNHG4 knockdown on CD4+ T cells.

Conclusion: LncRNA SNHG4 sponges miR-144-3p and upregulates MET to promote the proliferation, colony formation, invasion, and immune escape of CRC cells, leading to the progression of CRC.

Keywords: LncRNA SNHG4; MET; colorectal cancer; immune escape; miR-144-3p.