CHKB-AS1 enhances proliferation and resistance to NVP-BEZ235 of renal cancer cells via regulating the phosphorylation of MAP4 and PI3K/AKT/mTOR signaling

This study aims to elucidate these aspects, enhancing our understanding of NVP-BEZ235's future clinical utility. To investigate resistance mechanisms, renal cancer cell lines were exposed to progressively increasing concentrations of NVP-BEZ235, leading to the development of stable resistance. These resistant cells underwent extensive RNA-sequencing analysis. We implemented gene interference techniques using plasmid vectors and lentivirus and conducted regular IC50 assessments. To pinpoint the role of LncRNAs, we utilized FISH and immunofluorescence staining assays, supplemented by RNA pull-down and RIP assays to delineate interactions between LncRNA and its RNA-binding protein (RBP). Further, Western blotting and qRT-PCR were employed to examine alterations in signaling pathways, with an animal model providing additional validation. Our results show a marked increase in the IC50 of NVP-BEZ235 in resistant cell lines compared to their parental counterparts. A significant revelation was the role of LncRNA-CHKB-AS1 in mediating drug resistance. We observed dysregulated expression of CHKB-AS1 in both clinical samples of clear cell renal cell carcinoma (ccRCC) and cell lines. In vivo experiments further substantiated our findings, showing that CHKB-AS1 overexpression significantly enhanced tumor growth and resistance to NVP-BEZ235 in a subcutaneous tumorigenesis model, as evidenced by increased tumor volume and weight, whereas CHKB-AS1 knockdown led to a marked reduction in these...
Source: European Journal of Medical Research - Category: Research Source Type: research