Non-SMC condensin I complex subunit H promotes cell proliferation and inhibits cell apoptosis of clear cell renal cell carcinoma by activating the PI3K/AKT pathway.

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is a common cancer worldwide, frequently linked to unfavorable outcomes. The non-SMC condensin I complex subunit H (NCAPH) protein, one of the components of the non-structural maintenance of chromosomes (SMC) condensin I complex, plays a crucial part in regulating this complex, which is instrumental in the progression and advancement of various malignancies. Nonetheless, the significance of NCAPH in ccRCC is still not fully understood. This investigation was conducted to explore its potential impacts on ccRCC.

Methods: This investigation employed publicly available resources, such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, to evaluate the differential expression of NCAPH in ccRCC tumour tissues in comparison to corresponding normal tissues. Additionally, the study investigated the relationship between the prognostic model predicting overall survival (OS) and the advancement of ccRCC. An analysis was conducted on the genes expressed differently between groups with high and low NCAPH levels, followed by Gene Set Enrichment Analysis (GSEA) to gain further insights. Moreover, the presence of immune cell types within the context of NCAPH was also investigated. In addition to analyses from publicly available databases, assessments employing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot techniques were utilized to determine the levels of expression of NCAPH in ccRCC cell lines and tissue samples. Cell lines with stable NCAPH knockdown were created to further investigate its functional role. To evaluate cell growth, colony formation assays and Cell Counting Kit-8 (CCK-8) tests were performed. The analysis of the cell cycle and apoptosis was carried out using flow cytometry. Additionally, Western blot techniques were conducted to determine the levels of expression of proteins associated with apoptosis, cell cycle regulation, and the PI3K/AKT signaling pathway.

Results: An increase in NCAPH levels was observed in both tissues and cell lines derived from ccRCC. High levels of NCAPH were found to correlate with lower survival outcomes and a weakened immune response. The reduction of NCAPH levels could halt the progression of tumor cells during the G1 phase, which, in turn, greatly restricted their proliferation while promoting apoptosis. Additionally, it was shown that NCAPH could have an important role in activating the PI3K/AKT signaling pathway within ccRCC cells.

Conclusions: Individuals with ccRCC who demonstrated elevated levels of NCAPH were at an increased likelihood of experiencing poor prognostic outcomes. Moreover, NCAPH was crucial for promoting cellular growth and inhibiting apoptosis by activating the PI3K/AKT signaling pathway in ccRCC, suggesting its potential utility as both a marker for prognosis and a target for therapy.