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Archive > Volume 30 Issue 7 > 2023,30(7):586-593. DOI:10.3872/j.issn.1007-385X.2023.07.006 Prev Next
Basic Research
circSMARCA5 promotes non-small cell lung cancer cell proliferation via enrichment of Treg cells by CCL5
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Abstract:
Objective: To investigate the expression of circSMRCA5 in non-small cell lung cancer (NSCLC) tissues and cells and its potential function and mechanism in the occurrence and development of NSCLC. Methods: The expression of circSMARCA5 in NSCLC tissues was detected by qPCR. The circSMARCA5 over-expression plasmid and the control plasmid pLC5 were transfected into human lung cancer A549 and H1975 cells using the lentiviral transfection method, and the expression levels of circSMARCA5 in the stably transfected cell lines were detected by qPCR. The effects of circSMARCA5 over-expression on the biological behaviors of A549 and H1975 cells were examined by CCK-8, clone formation, cell cycle, and tumor xenografts. Mechanistically, transcriptome sequencing, KEGG and GO enrichment analysis were conducted to identify possible target genes of circSMARCA5. Subcutaneous xenograft models were constructed in BABL/c nude mice and immunocompetent C57 mice by using circSMARCA5-over-expressed NSCLC cells or Lewis cells. The effect of circSMARCA5 on the growth of subcutaneously transplanted tumors in nude mice was observed, and its effect on the contents of Treg cells in Lewis cells transplanted tumor tissues was detected by flow cytometry. Results: circSMARCA5 was highly expressed in NSCLC tissues (P<0.01). Over-expression of circSMARCA5 could promote the proliferation of NSCLC cells in vitro (P<0.05, P<0.01). In in vivo experiments,circSMARCA5 could promote the growth of the transplanted tumors in nude mice (P<0.01). Mechanistically, C-C chemokine ligand 5 (CCL5) was identified as a downstream target gene of circSMARCA5 by KEGG and GO enrichment analysis. The expression of CCL5 was increased in A549 and H1975 cells of circSMARCA5 over-expression group (P<0.05). circSMARCA5-mediated upregulation of CCL5 promoted the growth of subcutaneous tumors in immunocompetent C57 mice. Flow cytometry of single-cell suspensions prepared from subcutaneous tumors of C57 mice showed that the proportion of Treg cells in the circSMARCA5 over-expression group was higher than that in the control group ([3.1±0.5]% vs [1.0±0.1]%, P<0.05). Conclusion: circSMARCA5 is highly expressed in NSCLC tissues. circSMARCA5 may recruit Treg cells via CCL5, leading to the immune escape of tumors and promoting the progression of NSCLC.
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