LncRNA PVT1 influences breast cancer cells glycolysis through sponging miR-145-5p

Huan Qu; Xingxing Li; Fei Chen; Min Zhang; Xun Lu; Yun Gu; Mingming Lv; Cheng Lu

doi:10.1007/s13258-023-01368-8

LncRNA PVT1 influences breast cancer cells glycolysis through sponging miR-145-5p

Genes Genomics. 2023 May;45(5):581-592. doi: 10.1007/s13258-023-01368-8. Epub 2023 Mar 20.

Authors

Huan Qu^{1

2}, Xingxing Li¹, Fei Chen¹, Min Zhang¹, Xun Lu³, Yun Gu⁴, Mingming Lv⁵, Cheng Lu⁶

Affiliations

¹ Department of Breast, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123rd Tianfei Street, Mochou Road, Nanjing, 210004, China.
² Department of Health Management Centre, School of Medicine, Zhongda Hospital, Southeast University, Nanjing, 210009, China.
³ School of Public Health, Yale University, New Haven, CT, 06520, USA.
⁴ Department of Pathology, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, 210004, China.
⁵ Department of Breast, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123rd Tianfei Street, Mochou Road, Nanjing, 210004, China. jinanmingming@126.com.
⁶ Department of Breast, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123rd Tianfei Street, Mochou Road, Nanjing, 210004, China. lucheng_njmu@163.com.

Abstract

Background: Long-non-coding RNA PVT1 (lncRNA PVT1) can be used as an oncogenic regulatory non-coding RNA (ncRNA) for many cancers. However, its function and mechanism in breast cancer (BRCA) are still not clearly elucidated.

Objective: We attempt to explain the mechanism of PVT1's role in breast cancer from different perspectives.

Methods: We analyzed the expression of PVT1 and its correlation with the breast cancer related clinical data in the The Cancer Genome Atlas (TCGA) database. We used PVT1 overexpression and knockdown lentivirus to infect breast cancer MDA-MB-231 cell line for cell function verification, in vitro using CCK-8 to measure proliferation, flow cytometry to measure apoptosis, transwell test to measure invasion and migration ability, detecting cell extracellular acidification rate (ECAR) to assess glycolysis metabolism and explore the biological functions of PVT1 in breast cancer cells. Transcriptome sequencing was used to analyze the changes of related genes in cells after overexpression of PVT1. In vivo we used a xenograft model to study the effect of PVT1 on breast cancer.

Results: PVT1 was up-regulated in breast cancer tissues and was positively correlated with the clinical stage of breast cancer patients. Overexpression of PVT1 in vitro promoted cell proliferation, migration and invasion, and promoted tumor growth in vivo. Knockdown of PVT1 led to the opposite biological consequence. Further bioinformatics analysis showed that PVT1 changes the glycolysis metabolism of tumors through regulation of glycolysis-related genes. In addition, the expression of miR-145-5p is negatively correlated with PVT1. We consider the possibility of PVT1 promoting cell proliferation and metastasis by regulating the aerobic glucose metabolism in breast cancer cells through sponging the miR-145-5p.

Conclusion: Our results reveal a potential pathway for competing endogenous RNA to regulate breast cancer glucose metabolism. PVT1 regulates glycolysis related genes expression by competitively binding to endogenous miR-145-5p in breast cancer cells to change the metabolic phenotype. This may Provide new ideas for precise molecular therapy targets for breast cancer.

Keywords: Breast cancer; Glycolysis; LncRNA PVT1; miR-145-5p.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / genetics
Cell Line, Tumor
Female
Glucose
Glycolysis / genetics
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
RNA, Long Noncoding* / metabolism

Substances

MicroRNAs
RNA, Long Noncoding
Glucose
MIRN145 microRNA, human