Background: N6-methyladenosine (m6A) is the most prevalent RNA modification. While the role of m6A in prostate cancer remains unknown. We aim to measure the effects of m6A methylation regulatory genes during the development and progression of prostate cancer. Methods: We collected transcriptome information and gene-level alteration data from The Cancer Genome Atlas datasets. The log-rank test and Cox regression model were used to examine the prognosis value of m6A methylation regulatory genes of prostate cancer. Results: We discovered that most of m6A methylation regulators were highly expressed in aggressive prostate cancer. Univariable and multivariable Cox regression results showed that the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) and N6-adenosine-methyltransferase non-catalytic subunit (METTL14) and copy number variant of AlkB Homolog 5 (ALKBH5) were considerably associated with a recurrence-free survival of prostate cancer. Furthermore, a high level of m6A methylation in mRNA promotes the progression of prostate cancer via regulating subcellular protein localization. Conclusion: Patients with a high level of mRNA methylation resulted from overexpression of reader proteins and methyltransferase complexes had poor survival benefits through influencing protein subcellular location in prostate cancer.

properties with low immunogenicity and the infiltration of T cells. [3] Therefore, strategies by which "cold" tumors can be transformed into "hot" tumors have been extensively researched so that more patients may obtain the benefits of ICBs therapy. The immunogenic cell death (ICD) of tumors has been proved to be an effective tool to improve the immunogenicity of tumor cells. [4] ICD occurs when specific inducers harness the host immune system to recognize and kill cancer cells by causing endoplasmic reticulum (ER) stress. [5] The dying tumor cells release damage-associated molecular patterns (DAMPs), which primarily consist of calreticulin (CRT), high mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and heat shock protein 70 (HSP70). [6] Previous literature revealed that the antigen presentation efficiency of dendritic cells (DCs) was positively correlated with the DAMP content in tumors; [7] therefore, the sufficient release of DAMPs from tumor cells undergoing ICD is crucial to improve immunotherapy efficiency. Apart from the low immunogenicity of tumor cells, the counteracted innate immune system is also responsible for the poor therapeutic effect of ICBs. The suppressive immune cells in tumors, including tumor-associated macrophages (TAMs) and regulatory T cells (Tregs), always lead to immunotherapy failure because they limit T cell infiltration Immunogenic cell death (ICD) has aroused widespread attention because it can reconstruct a tumor microenvironment and activate antitumor immunity. This study proposes a two-way enhancement of ICD based on aCaO 2 @CuS-MnO 2 @HA (CCMH) nanocomposite to overcome the insufficient damageassociated molecular patterns (DAMPs) of conventional ICD-inducers. The near-infrared (NIR) irradiation (1064 nm) of CuS nanoparticles generates 1 O 2 through photodynamic therapy (PDT) to trigger ICD, and it also damages the Ca 2+ buffer function of mitochondria. Additionally, CaO 2 nanoparticles react with H 2 O to produce a large amount of O 2 and Ca 2+ , which respectively lead to enhanced PDT and Ca 2+ overload during mitochondrial damage, thereby triggering a robust ICD activation. Moreover, oxidative-damaged mitochondrial DNA, induced by PDT and released from tumor cells, reprograms the immunosuppressive tumor microenvironment by transforming tumor-associated macrophages to the M1 subphenotype. This study shows that CCMH with NIR-II irradiation can elicit adequate DAMPs and an active tumorimmune microenvironment for both 4T1 and CT26 tumor models. Combining this method with an immune checkpoint blockade can realize an improved immunotherapy efficacy and long-term protection effect for body.

Objectives Paeoniflorin, a representative pinane monoterpene glycoside in plants of Paeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancers in vivo and in vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations. Key findings Anticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential molecular mechanisms corresponding to the antitumour effects of Paeoniflorin might be related to the following aspects: inhibition of tumour cell proliferation and neovascularization, induction apoptosis, and inhibition of tumour invasion and metastasis. Summary Paeoniflorin has wide spectrum antitumour activities; however, in vivo and clinical investigations on antitumour effect of Paeoniflorin are lacking which should be focused on further studies. Our present review on antitumour effects of Paeoniflorin would be beneficial for the further molecular mechanisms study, candidate antitumour drug development and clinical research of Paeoniflorin in the future.