Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-methylguanosine (mG) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of mG tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed mG tRNA methylation in cancer cell translation control and tumour biology.
PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment.
Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC).
Radiosensitivity is critical for clinical outcomes and overall survival of prostate cancer patients treated with irradiation. Ribociclib and NU7026 have been reported as radiosensitizers in cancer cells, but which are inadequately understood in prostate cancer cells. The present study was performed to investigate the effects of ribociclib, NU7026, and their combination on the radiosensitivity of prostate cancer cells.
Purpose: The reduced cardiorespiratory fitness (CRF) and functional capacity following surgical procedures and during cancer treatments is a major risk factor for morbidity and mortality among patients with cancer. We aimed to assess the impact of endurance and combined resistance exercise interventions during the postoperative rehabilitation period for patients with colorectal, breast, and prostate cancer.
Methods: A systematic search was conducted in MEDLINE Pubmed, Web of Science, and Cochrane Library until October 2023 for randomized controlled trials that assessed exercise interventions (aerobic/endurance; resistance or combined training) on postoperative patients with cancer.
