NCAPH promotes glucose metabolism reprogramming and cell stemness in ovarian cancer cells through the MEK/ERK/PD-L1 pathway.

BACKGROUNDS

Ovarian cancer is a prevalent malignant tumor that affects the female reproductive system with the characteristic of high heterogeneity. Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) has been implicated in a variety of cancers.

METHODS

The expression of NCAPH before and after transfection were assessed using RT-qPCR and western blot analysis. Cell stemness was evaluated through spheroid formation assay. The extracellular acidification rate (ECAR) of ovarian cancer cells was measured utilizing Seahorse Glycolysis Stress Test Assay while oxygen consumption rate (OCR) was estimated with Seahorse Mito Stress Test Assay. Lactate production and glucose consumption were quantified using corresponding assay kits. Western blot was employed to analyze the expression of stem cell markers, glycolysis- and MEK/ERK/PD-L1 signaling pathway-related proteins. In vivo, tumor size and weight were recorded, and immunohistochemical staining was used to assess MEK/ERK/PD-L1 and KI67 expression in tumor tissues from nude mice.

RESULTS

It was observed that NCAPH expression is upregulated in ovarian cancer cells. Silencing NCAPH led to repression of both stemness characteristics and glucose metabolism reprogramming. Furthermore, knockdown of NCAPH inhibited the MEK/ERK/PD-L1 signaling pathway both in vitro and in vivo, resulting in suppressed tumor growth in mouse models.

CONCLUSION

Collectively, silencing NCAPH impedes malignant progression of ovarian cancer through modulation of the MEK/ERK/PD-L1 pathway.

CLINICAL TRIAL NUMBER

Not applicable.