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Effect of CXCR2 Deficiency in HeLa Cell on the Regulatory Network of Coding Genes and Non-Coding RNAs
Wei Dong1,2,3, Jifang Gao1,2,3, Yilin Mu4
1Department of Laboratory Medicine, Linyi People's Hospital, Linyi, Shandong, China.
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.
Insights
CXCR2 deficiency in HeLa cells significantly alters mRNA, lncRNA, and circRNA expression, impacting tumor and cytokine signaling pathways. These findings offer new targets for cervical cancer research.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- C-X-C motif chemokine receptor 2 (CXCR2) is integral to inflammation and immunity.
- Chemokine receptors are known to influence the tumor microenvironment.
- The comprehensive impact of CXCR2 deficiency on tumor cell transcriptomes, including mRNA and non-coding RNAs (ncRNAs), remains largely uncharacterized.
Purpose of the Study:
- To investigate the global transcriptomic alterations in CXCR2 knockout HeLa cells.
- To identify differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs).
- To construct potential regulatory networks influenced by CXCR2 deficiency.
Main Methods:
- Transcriptome sequencing of CXCR2 knockout HeLa cells compared to control cells.
- Identification of differentially expressed mRNAs, lncRNAs, and circRNAs.
- Validation of selected differentially expressed molecules using real-time PCR and Sanger sequencing.
Main Results:
- Identification of 1306 differentially expressed coding genes, 397 lncRNAs, and 846 circRNAs.
- Specific differentially expressed genes (e.g., ARHGEF4, CACNA2D3, FHIT) and ncRNAs were validated.
- These alterations suggest a role for CXCR2 in tumor development and progression.
Conclusions:
- CXCR2 deficiency profoundly impacts the expression profiles of coding genes and ncRNAs in HeLa cells.
- Altered gene and ncRNA expression is linked to tumor and cytokine signaling pathways.
- The study provides potential insights into mechanisms driving cervical cancer and identifies novel research targets.
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