CXCL1 Regulated by miR-302e Is Involved in Cell Viability and Motility of Colorectal Cancer via Inhibiting JAK-STAT Signaling Pathway

Biyin Chen; Li Song; Xiuzhen Nie; Fangfeng Lin; Zongyang Yu; Wencui Kong; Xiaoyan Qi; Wenwu Wang

doi:10.3389/fonc.2020.577229

CXCL1 Regulated by miR-302e Is Involved in Cell Viability and Motility of Colorectal Cancer via Inhibiting JAK-STAT Signaling Pathway

Front Oncol. 2021 May 17:10:577229. doi: 10.3389/fonc.2020.577229. eCollection 2020.

Authors

Biyin Chen¹, Li Song¹, Xiuzhen Nie¹, Fangfeng Lin¹, Zongyang Yu², Wencui Kong², Xiaoyan Qi³, Wenwu Wang¹

Affiliations

¹ Department of Oncology, The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China.
² Department of Pulmonary and Critical Care Medicine, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China.
³ Department of Oncology, Zibo Central Hospital, Zibo, China.

Abstract

Purpose: This study made a systemic description for the CXCL1-dependent regulatory mechanism in colorectal cancer (CRC).

Methods: Bioinformatics methods were applied to obtain target mRNA CXCL1 and corresponding upstream miRNA. qRT-PCR and Western blot were performed to measure the levels of CXCL1 and miR-302e in CRC tissue and cells. Experiments including CCK-8, wound healing assay, Transwell invasion assay, and flow cytometry were conducted to assess cell biological behaviors. Dual-luciferase reporter assay was carried out for verification of the targeting relationship between CXCL1 and miR-302e. The inhibitor AG490 of JAK-STAT signaling pathway was used to identify the functional mechanism of CXCL1/JAK-STAT underlying progression of CRC, and tumor xenograft experiments were performed for further validation.

Results: CXCL1 was highly expressed in CRC tissue and cells, while miR-302e was poorly expressed. Silencing CXCL1 or overexpressing miR-302e could lead to inhibition of cell proliferation, migration, invasion but promotion of cell apoptosis of CRC. Besides, CXCL1 was identified as a direct target of miR-302e, and CXCL1 could reverse the effect of miR-302e on cell proliferation, migration, invasion, and apoptosis. Furthermore, CXCL1 functioned on CRC cell biological behaviors via activation of JAK-STAT signaling pathway.

Conclusion: CXCL1 could be regulated by miR-302e to inactivate JAK-STAT signaling pathway, in turn affecting cell proliferation, migration, invasion, and apoptosis of CRC. Our result provides a potential therapeutic target for CRC treatment.

Keywords: chemokine ligand-1; colorectal cancer; janus kinase signal transducer and activator of transcription; miR-302e; migration and invasion; proliferation.