MYB Proto-Oncogene Like 2 Promotes the Growth of Renal Carcinoma by Attenuating Endoplasmic Reticulum Stress and Activating Lipid Rafts.

Objective: Renal cell carcinoma (RCC) is a typical malignant lesion of kidney with high recurrence rate and high mortality. MYB proto-oncogene-like 2 (MYBL2) is significantly expressed in cancer cells and closely linked to cancer development and poor prognosis. This study aimed to investigate the role and possible mechanisms of MYBL2 in renal cancer.

Method: MYBL2 was silenced and overexpressed in A498 kidney cancer cells. The ability of A498 cells to migrate and proliferate was analysed by 5-ethynyl-2'-deoxyuridine staining, colony formation assay, Transwell assay and cell counting kit-8 assay. Endoplasmic reticulum stress was assessed by boron-dipyrromethene (BODIPY) staining, and the messenger ribonucleic acid (mRNA) levels of endoplasmic reticulum (ER) stress markers were determined. Cholesterol levels in A498 cells were analysed by measuring total cholesterol, free cholesterol and Filipin III staining. Sphingomyelin levels were measured, and cholera toxin subunit B (CT-B) staining was used to analyse the stability of lipid rafts. The relationship between MYBL2 and ER stress was confirmed using the ER stress inhibitor 4-phenylbutyric acid.

Results: MYBL2 promotes the proliferation and migration of A498 cells (p < 0.01), inhibits the glucose regulated protein 78kD (GRP78)-protein kinase r-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2 alpha (eIF2α)-activating transcription factor 4 (ATF4)-C/EBP-homologous protein (CHOP) axis (p < 0.01) and ER stress (p < 0.001), upregulates cholesterol levels and increases lipid raft stability (p < 0.001).

Conclusions: This study highlights the potential of MYBL2 as a therapeutic target for renal cancer. It is a novel oncogene that stimulates the growth of renal cancer cell A498 by reducing ER stress and triggering lipid raft regulation.