Overexpression of YTHDC2 contributes to the progression of prostate cancer and predicts poor outcomes in patients with prostate cancer

Abstract

YTH domain‐containing protein 2 (YTHDC2), a member of N6‐methyladenosine (m6A) readers, has been reported to be closely associated with multiple cancer types. However, very little is known about the YTHDC2 gene and its involvement in prostate cancer. YTHDC2 protein expression level was analyzed and correlated to clinical outcomes in prostate cancer patients who underwent prostatectomy in Guizhou Provincial People's Hospital. The YTHDC2 expression level was also detected in prostate cancer cell lines and an immortalized prostate epithelial cell line BPH‐1 and RWPE1 by quantitative real‐time reverse transcription polymerase chain reaction. Furthermore, we established stable cell lines (DU145 and PC‐3) transfected with either empty vector or the full‐length YTHDC2 gene and conducted cell function assays in vitro. Fisher's exact test and Pearson χ2 test were employed, Kaplan–Meier method was used for the survival analysis. Of 32 patient samples who enrolled in this study, YTHDC2 was significantly upregulated in prostate cancer (PCa) patients with higher Gleason scores and serum prostate‐specific antigen levels. YTHDC2 expression was significantly elevated in all PCa cell lines compared to BPH‐1 and RWPE1 (all p < 0.05). Functionally, the enforced expression of YTHDC2 markedly promoted cell growth, migration, and invasion efficacies in prostate cancer cells. Our data indicate that YTHDC2 upregulation may be potentially associated with the prognosis of prostate cancer patients.

The role of RNA modification in urological cancers: mechanisms and clinical potential

“…YTHDC1 was found to bind and colocalize with oncogene MET adhesin in subnuclear patches and affect PCa proliferation [ 186 ]. YTHDC2 expression was upregulated in PCa tissues and cell lines and significantly correlated with PSA levels and Gleason scores, whereas YTHDC2 overexpression promoted proliferation and invasion in PCa cell lines [ 187 ]. It was also discovered that YTHDF1/2 was overexpressed in PCa, and PLK1, a critical cell cycle factor, is a direct target of YTHDF1 in PCa cells.…”

Ramifications of m6A Modification on ncRNAs in Cancer

“…IGF2BP1-3 have been also been with the progression of various cancers (117)(118)(119). Other readers of m6A methylation including YTHDC1/2, ELAVL1 and hnRNPs also affect the progression of cancer by regulating a number of important genes implicated in tumorigenesis (120)(121)(122)(123)(124). Anomalies in expression of m 6 A regulating molecules has been associated with a poor prognosis, therapy resistance and impaired antitumour immunity in various cancer types (125,126).…”