CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis

Xiyu Dai; Xinan Chen; Wensun Chen; Yuxi Ou; Yiling Chen; Siqi Wu; Quan Zhou; Chen Yang; Limin Zhang; Haowen Jiang

doi:10.1080/15592294.2023.2178802

CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis

Epigenetics. 2023 Dec;18(1):2178802. doi: 10.1080/15592294.2023.2178802.

Authors

Xiyu Dai^{1

2}, Xinan Chen^{1

2}, Wensun Chen^{1

2}, Yuxi Ou^{1

2}, Yiling Chen^{1

2}, Siqi Wu^{1

2}, Quan Zhou^{1

2}, Chen Yang^{1

2

3}, Limin Zhang^{1

2

3}, Haowen Jiang^{1

2

3}

Affiliations

¹ Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
² Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
³ National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, China.

Abstract

Prostate cancer is the most prevalent type of cancer among men worldwide. The importance of circular RNA (circRNA) in prostate cancer and its connection to malignancy has been steadily recognized. circRNA expression was obtained by circRNA sequencing of prostate cancer. circRNA and its function were further analysed. The results were verified by qRT-PCR, RIP assay, FISH, RNA pulldown, WB, CCK-8, colony formation assay and wound-healing assay. BALB/c Nude mice were used for xenograft hosts. Low expression of circDHRS3 was assessed in prostate cancer. Overexpression of circDHRS3 inhibited prostate cancer growth and migration in vitro. Additionally, miR-421 was shown to be the downstream target of circDHRS3, as shown by fluorescence in situ hybridization and dual-luciferase experiments. The rescue assay results for the PC3 and Du145 cell lines demonstrated that circDHRS3 inhibits prostate cancer cell lines' ability to proliferate and metastasize by modulating MEIS2 expression through the circDHRS3/miR-421/MEIS2 axis. In vivo investigations confirmed that the overexpression of circDHRS3 could inhibit both the lung and bone metastasis of prostate cancer cells. circDHRS3 has the potential to become a biomarker and a targeted therapeutic site for prostate cancer, particularly in the malignant stage. Our study indicates that circDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis.

Keywords: MEIS2; circDHRS3; circRNA; prostate cancer.

MeSH terms

Alcohol Oxidoreductases
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation / genetics
DNA Methylation
Gene Expression Regulation, Neoplastic
Homeodomain Proteins* / genetics
Humans
In Situ Hybridization, Fluorescence
Male
Mice
Mice, Nude
MicroRNAs* / genetics
Prostatic Neoplasms* / genetics
RNA, Circular* / genetics
Transcription Factors* / genetics

Substances

Homeodomain Proteins
MEIS2 protein, human
MicroRNAs
MIRN421 microRNA, human
RNA, Circular
Transcription Factors
Alcohol Oxidoreductases

Grants and funding

This work was supported by funds from the National Natural Science Foundation of China (No. 81872102 Haowen Jiang, No. 82002720 Limin Zhang, No. 82103215 Chen Yang).