PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway

Objective: To explore the effects of protein arginine methyltransferase 5 (PRMT5) on the biological function of breast cancer cells (BCCs) by regulating the liver X receptor alpha (LXR alpha)/NF-kappa Bp65 pathway. Methods: A total of 80 patients with breast cancer (BC) admitted to our hospital were collected, and 80 breast cancer tissue specimens and 80 corresponding tumor-adjacent tissue specimens were sampled from them for analysis. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of PRMT5 mRNA in the sampled tissues, and the Western blot to determine the expression of LXR alpha and NF-kappa Bp65 proteins in the tissues and cells. The patients were followed up to analyze their 3-year survival rate. Stable and transient overexpression vectors and inhibition vectors were constructed and transfected into BCCs. The cell counting kit-8 (CCK8), transwell, and flow cytometry were adopted to analyze the proliferation, invasion, and apoptosis of transfected cells, on which the effects of PRMT5 on LXR alpha and NF-kappa Bp65 proteins were analyzed. Results: PRMT5 was highly expressed in BC patients, and LXR alpha was lowly expressed in them, which had a high diagnostic value. Patients with high expression of PRMT5 showed a poor prognosis, and the expression of PRMT5 was related to the tumor size, pathological stage, differentiation, and metastatic in BC patients. Overexpressed PRMT5 enhanced the cell proliferation, invasion, and glycolysis abilities, weakened apoptosis ability, further lowered expression of LXR alpha and increased expression of NF-kappa Bp65, while inhibited PRMT5 caused opposite results in those aspects. Up-regulating the expression of LXR alpha suppressed the proliferation, invasion, and aerobic glycolysis of BCCs and promoted their apoptosis, while inhibiting it posed opposite effects. The rescue experiment revealed that down-regulating the expression of PRMT5 could counteract the promotion of down-regulation of LXR alpha on proliferation, invasion and glycolysis of BCCs, and the nude mouse tumorigenesis test revealed that PRMT5 induced tumor on nude mice by mediating LXR alpha/NF-kappa Bp65. Conclusion: Inhibition of the PRMT5 expression can accelerate apoptosis of BCCs and weaken their proliferation, invasion, and aerobic glycolysis through the LXR alpha/NF-kappa Bp65 pathway.