Effect of CXCR2 Deficiency in HeLa Cell on the Regulatory Network of Coding Genes and Non-Coding RNAs.

Objective: C-X-C motif chemokine receptor 2 (CXCR2) plays a crucial role in inflammation and immunity, and the involvement of chemokine receptors in the tumor microenvironment is extensively documented. However, the impact of CXCR2 deficiency on the complete transcriptome, including mRNA and ncRNAs, in tumor cells remains unclear.

Methods: In this study, we aimed to identify differentially expressed (DE) messenger RNA (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in CXCR2 knockout HeLa cells through transcriptome sequencing and to construct regulatory networks.

Results: Compared to control cells, differentially expressed mRNAs, lncRNAs and circRNAs, including 1306 coding genes, 397 lncRNAs, and 846 circRNAs were identified. Understanding these selected genes and ncRNAs could elucidate the influence of CXCR2 on tumor occurrence and progression. Furthermore, 6 DE genes, Rho guanine nucleotide exchange factor 4 (ARHGEF4), calcium voltage-gated channel auxiliary subunit alpha 2 delta 3 (CACNA2D3), fragile histidine triad (FHIT), potassium voltage-gated channel subfamily H member 5 (KCNH5), kelch like family member 1 (KLHL1) and teashirt zinc finger homeobox 2 (TSHZ2), 5 DE lncRNAs, CARMN, AL357060.1, AC098487.1, CECR7 and XLOC_009647, and 9 DE circRNAs, hsa_circ_0000196, hsa_circ_0000234, hsa_circ_0007976, hsa_circ_0008798, hsa_circ_0007766, hsa_circ_0116612, hsa_circ_0008012, hsa_circ_0004576 and hsa_circ_0118105 were verified using real-time PCR and sanger sequencing.

Conclusion: Transcriptome analysis revealed that CXCR2 deficiency in HeLa cells alters the expression of coding genes and ncRNAs involved in tumor and cytokine signaling. Overall, our findings offer potential insights into the mechanisms and new research targets for cervical cancer and other tumors.