LINC01134 regulates cell cycle and senescence to inhibit the proliferation of lung adenocarcinoma by competitively binding to CTCF and inhibiting CTCF-mediated p21 transcription

Long non-coding RNAs (lncRNAs) have garnered significant attention as potential therapeutic targets for treating lung adenocarcinoma (LUAD). This study focused on LINC01134, delving into the mechanism by which its overexpression promoted the proliferation of A549 cells. Gene set enrichment analysis (GSEA) revealed significant enrichment of LINC01134 in p21 pathway. Bioinformatics screening highlighted the role of the transcription factor CTCFas a potential candidate for mediating the connection between LINC01134 and p21. Cell proliferationand cycle were assessed using CCK-8, colony formation and Flow cytometry. SA-β-galactosidase staining kit was used to assess cellular senescence. Optical microscopy was done to examine cell morphology. Cell cycle-related proteins were analyzed using Western blotting to observe the effects of LINC01134 overexpression on the cell cycle, senescence, and proliferation. The aforementioned methods were employed to detect LINC01134-mediated regulation of p21 on cell cycle, senescence, and proliferation, and the LINC01134-mediated regulation of CTCF on p21, cell cycle, senescence, and proliferation. RNA pulldown and RIP were conducted to detect interaction between LINC01134 and CTCF. ChIP was used to measure CTCF-p21 interactions and the effect of LINC01134 overexpression on this direct interaction. FISH was used to assess the effect of LINC01134 overexpression on the colocalization of CTCF protein and p21 DNA. The results confirmed that LINC01134 competitively interacted with CTCF to inhibit CTCF-mediated transcription of p21to accelerate G1/S cycle transition, delay cellular senescence, and promote the proliferation of A549 cells. LINC01134 is anticipated to serve as a potential biomarker for recurrence and prognosis in patients with LUAD.