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. 2020 Apr 21:13:3347-3357.
doi: 10.2147/OTT.S239730. eCollection 2020.

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

Xiao Han  1 , Linlin Wei  2 , Bin Wu  3
Affiliations

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

Xiao Han et al. Onco Targets Ther. .

Abstract

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 α (LXRα)/NF-κBp65 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 LXRα and NF-κBp65 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 LXRα and NF-κBp65 proteins were analyzed.

Results: PRMT5 was highly expressed in BC patients, and LXRα 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 LXRα and increased expression of NF-κBp65, while inhibited PRMT5 caused opposite results in those aspects. Up-regulating the expression of LXRα 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 LXRα on proliferation, invasion and glycolysis of BCCs, and the nude mouse tumorigenesis test revealed that PRMT5 induced tumor on nude mice by mediating LXRα/NF-κBp65.

Conclusion: Inhibition of the PRMT5 expression can accelerate apoptosis of BCCs and weaken their proliferation, invasion, and aerobic glycolysis through the LXRα/NF-κBp65 pathway.

Keywords: LXRα; NF-κ BP65; PRMT5; biological function; breast cancer cell.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The expression of PRMT5 in breast cancer and its clinical significance; (A) The expression of PRMT5 mRNA in breast cancer tissues; (B) The expression of PRMT5 protein in breast cancer tissues; (C) The expression of PRMT5 mRNA in breast cancer cells; (D) The expression of PRMT5 protein in breast cancer cells; (E) Prognosis of patients with different PRMT5 expression. aIndicates P<0.05.
Figure 2
Figure 2
The effects of PRMT5 on the biological function of breast cancer cells; (A) The expression of PRMT5 mRNA in breast cancer cells after transfection; (B) The effects of PRMT5 on the proliferation of breast cancer cells; (C) The effects of PRMT5 on the invasive ability of breast cancer cells; (D) The effects of PRMT5 on the apoptosis of breast cancer cells; (E) The effects of PRMT5 on apoptosis-related proteins in breast cancer cells. aIndicates P<0.05.
Figure 3
Figure 3
The effects of PRMT5 on aerobic glycolysis of breast cancer cells and LXRα/NF-κBp65 pathway; (A) The effects of PRMT5 on glucose consumption of breast cancer cells; (B) The effects of PRMT5 on lactic acid of breast cancer cells; (C) The effects of PRMT5 on aerobic glycolysis-related proteins in breast cancer cells; (D) The effects of PRMT5 on the LXRα/NF-κBp65 pathway of breast cancer cells. aIndicates P<0.05.
Figure 4
Figure 4
The effects of LXRα on the biological function and aerobic glycolysis of breast cancer cells; (A) The expression of LXRα protein in breast cancer cells after transfection; (B) The expression of NF-κBp65 protein in breast cancer cells after transfection; (C) The effects of LXRα on breast cancer cells; (D) The effects of LXRα on the invasion of breast cancer cells; (E) The effects of LXRα on the apoptosis of breast cancer cells; (F) The effects of LXRα on apoptosis-related proteins in breast cancer cells; (G) The effects of LXRα on aerobic glycolysis in breast cancer cells. aIndicates P<0.05.
Figure 5
Figure 5
The effects of co-transfection of Si-PRMT5 and Si-LXRα on breast cancer cells; (A) The effects of co-transfection of Si-PRMT5 and Si-LXRα on the proliferation of breast cancer cells; (B) The effects of co-transfection of Si-PRMT5 and Si-LXRα on glucose consumption of breast cancer cells; (C) The effects of co-transfection of Si-PRMT5 and Si-LXRα on lactic acid of breast cancer cells; (D) The effects of co-transfection of Si-PRMT5 and Si-LXRα on the invasion of breast cancer cells; (E) The effects of co-transfection of Si-PRMT5 and Si-LXRα on the apoptosis of breast cancer cells; (F) The effects of co-transfection of Si-PRMT5 and Si-LXRα on apoptosis-related proteins of breast cancer cells; (G) The effects of co-transfection of Si-PRMT5 and Si-LXRα on aerobic glycolysis of breast cancer cells. aIndicates P<0.05.
Figure 6
Figure 6
PRMT5 promotes the tumor formation in nude mice by mediating LXRα/NF-κBp65; (A) Changes of subcutaneous tumor volume in nude mice after 28 d days. (B). The tumor volume of nude mice after 28 days. (C) The expression of LXRα protein and NF-κBp65 protein in tumor tissues of nude mice. aIndicates P<0.05.
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