Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel

Mingyue Xia; Shuyan Wang; Yannan Qi; Kaili Long; Enjie Li; Lingfeng He; Feiyan Pan; Zhigang Guo; Zhigang Hu

doi:10.3389/fonc.2022.993243

Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel

Front Oncol. 2022 Nov 10:12:993243. doi: 10.3389/fonc.2022.993243. eCollection 2022.

Authors

Mingyue Xia¹, Shuyan Wang¹, Yannan Qi¹, Kaili Long¹, Enjie Li¹, Lingfeng He¹, Feiyan Pan¹, Zhigang Guo¹, Zhigang Hu¹

Affiliation

¹ Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.

Abstract

The expression of O-GlcNAc transferase (OGT) and its catalytic product, O-GlcNAcylation (O-GlcNAc), are elevated in many types of cancers, including prostate cancer (PC). Inhibition of OGT serves as a potential strategy for PC treatment alone or combinational therapy. PC is the second common cancer type in male worldwide, for which chemotherapy is still the first-line treatment. However, the function of inhibition of OGT on chemotherapeutic response in PC cells is still unknown. In this study, we show that inhibition of OGT by genetic knockdown using shRNA or by chemical inhibition using OGT inhibitors sensitize PC cells to docetaxel, which is the most common chemotherapeutic agent in PC chemotherapy. Furthermore, we identified that microRNA-140 (miR-140) directly binds to OGT mRNA 3' untranslated region and inhibits OGT expression. Moreover, docetaxel treatment stimulates miR-140 expression, whereas represses OGT expression in PC cells. Overexpression of miR-140 enhanced the drug sensitivity of PC cells to docetaxel, which could be reversed by overexpression of OGT. Overall, this study demonstrates miR-140/OGT axis as therapeutic target in PC treatment and provides a promising adjuvant therapeutic strategy for PC therapy.

Keywords: OGT; chemotherapy; docetaxel; miR-140; prostate cancer.