Long non-coding RNA PVT1 promotes cell proliferation in ERα+ breast cancer through the ERα-BTG2 axis

Abstract

Background: Plasmacytoma variant translocation 1 (PVT1) is recognized as an oncogenic long non-coding RNA (lncRNA) in multiple cancer types including breast cancer (BC). Estrogen receptor alpha-positive (ERα+) BC is the major BC subtype, accounting for about 70% of cases. However, the role of PVT1 in this subtype and the underlying mechanisms are not yet fully elucidated.

Objective: To investigate the clinical significance and biological function of PVT1 in ERα+ BC.

Methods: The expression level and prognosis significance of PVT1 in ERα+ BC was explored through in silico analysis based on public databases. The biological function of PVT1 in ERα+ BC was examined in MCF7, a typical ERα+ BC cell line. MTS, plate clone formation and EdU assay were used to detect the effect of PVT1 knockdown on BC cell proliferation. The impact of PVT1 knockdown on estrogen signaling was assessed by measuring the expression of ERα and its downstream molecules through quantitative real-time PCR (qRT-PCR) and/or western blot. The regulatory effect of PVT1 on ERα was further investigated using protein stability experiments. To confirm the role of ERα in PVT1-regulated cell proliferation, rescue assay was conducted by targeting its downstream molecule BTG2.

Results: PVT1 expression is elevated in BC tissues compared to adjacent non-cancerous tissues, particularly in the ERα+ subtype. PVT1 knockdown substantially inhibited the proliferation of MCF7 cells as well as the estrogen signaling, which was evidenced by the marked downregulation of ERα and its downstream molecules including TFF1 and GREB1. Mechanistically, PVT1 knockdown was proved to significantly accelerate the degradation of ERα protein. BTG2 is a downstream molecule negatively regulated by ERα, which was upregulated upon PVT1 knockdown. In the rescue assay, interference of BTG2 could largely attenuated the inhibitory effect of PVT1 knockdown on cell proliferation.

Conclusion: PVT1 knockdown could inhibit cell proliferation partly through disrupting the ERα-BTG2 axis in ERα+ breast cancer.

Keywords

Breast cancer / PVT1 / Estrogen receptor alpha / Proliferation

Declarations

Not applicable.

CRediT authorship contribution statement

Haibo Zhang: Conceptualization, Methodology, Investigation. Haibo Zhang, Shuoguo Tan: Data curation, Formal analysis, Visualization. Ying Zeng, Junli Deng, Yarui Liu: Writing - original draft. Rui Liang, Li Nan, Xiaomei Zhou, Guoying Fang: Writing - review & editing. Guo Wang: Validation, Supervision.

Ethics approval and consent to participate

This article uses publicly available database data and does not involve ethical approval or informed consent.

Consent for publication

All authors have read and agreed to the published version of the manuscript and give their consent for publication in this journal.

Availability of data and materials

Not applicable.

Funding

This study was supported by the Zhejiang Provincial Medical and Health Science and Technology Plan (No. 2024KY225), the National Natural Science Foundation of China (No. 81673516 and No. 82003870), the Guangzhou Science and Technology Program Project (No. 2024A04J4883), the Maternal and Child Health Hospital of Hubei Province Research Project (No. 2021SFYY003), and the Scientific and Technological Innovation Team Building Program of Suzhou Vocational Health College (No. SZWZYTD202205).

Declarations of Competing Interest

The authors declare no competing interests.

Acknowledgements

Not applicable.

Authors' other information

Not applicable.

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