In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive mitophagy lead to an increase in defective mitochondria and ultimately exacerbate MIRI by causing overproduction or uncontrolled production of mitochondria. Phosphatase and tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing 1 (FUNDC1) and B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators of mitophagy in MIRI. Pink1 and Parkin are mitochondrial surface proteins involved in the ubiquitin-dependent pathway, while BNIP3 and FUNDC1 are mitochondrial receptor proteins involved in the non-ubiquitin-dependent pathway, which play a crucial role in maintaining mitochondrial homeostasis and mitochondrial quality. These proteins can induce moderate mitophagy or inhibit excessive mitophagy to protect against MIRI but may also trigger excessive mitophagy or insufficient mitophagy, thereby worsening the condition. Understanding the actions of these mitophagy mechanistic proteins may provide valuable insights into the pathological mechanisms underlying MIRI development. Based on the above background, this article reviews the mechanism of mitophagy involved in MIRI through Pink1/Parkin pathway and the receptor mediated pathway led by FUNDC1 and BNIP3, as well as the related drug treatment, aim to provide effective strategies for the prevention and treatment of MIRI.

Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients’ survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT–DNA–PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN–ATM–CHK2 signal and ATR–CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.

Metformin is one of the most commonly used first-line oral medications for type 2 diabetes mellitus. Multiple observational studies, reviewed in numerous systematic reviews, have shown that metformin treatment may not only reduce the risk of cancer but may also improve the efficacy of cancer treatment in diabetic patients. Recent studies have been conducted to determine whether a similar protective effect can be demonstrated in nondiabetic cancer patients. However, the results are controversial. The potential optimal dose, schedule, and duration of metformin treatment and the heterogeneity of histological subtypes and genotypes among cancer patients might contribute to the different clinical benefits. In addition, as the immune property of metformin was investigated, further studies of the immunomodulatory effect of metformin on cancer cells should also be taken into account to optimize its clinical use. In this review, we present and discuss the latest findings regarding the anticancer potential of metformin in nondiabetic patients with cancer.

Radiogenomics is the whole genome application of radiogenetics, which focuses on uncovering the underlying genetic causes of individual variation in sensitivity to radiation. There is a growing consensus that radiosensitivity is a complex, inherited polygenic trait, dependent on the interaction of many genes involved in multiple cell processes. An understanding of the genes involved in processes such as DNA damage response and oxidative stress response, has evolved toward examination of how genetic variants, most often, single nucleotide polymorphisms (SNPs), may influence interindividual radioresponse. Many experimental approaches, such as candidate SNP association studies, genome-wide association studies and massively parallel sequencing are being proposed to address these questions. We present a review focusing on recent advances in association studies of SNPs to radiotherapy response and discuss challenges and opportunities for further studies. We also highlight the clinical perspective of radiogenomics in the future of personalized treatment in radiation oncology.