Clear cell renal cell carcinoma (ccRCC) predominantly originates from renal tubular epithelial cells and displays resistance to conventional chemotherapy and radiation therapy. Multi-omics studies have delineated the intimate correlation between the molecular characteristics of ccRCC and chromosomal alterations, suggesting that interventions targeting DNA damage repair (DDR) could potentially enhance patient prognosis. This comprehensive review encompasses ccRCC epidemiology, clinical classification, diagnosis, and therapeutic strategies, with a focus on its molecular mechanisms and tumor microenvironment (TME). Special emphasis is placed on the role of DDR in ccRCC development, summarizing the latest advances in our understanding of key pathways, including mismatch repair, base excision repair, nucleotide excision repair, non-homologous end joining, and homologous recombination repair. Furthermore, the review addresses the challenges associated with current treatment approaches, such as the adaptability and resistance of ccRCC to vascular endothelial growth factor (VEGF) inhibitors and mTOR pathway inhibitors, while also exploring emerging strategies for targeting DDR in ccRCC.

The tumor microenvironment, tissue origin, stage, and subtype can influence mitochondrial function. This study investigated the impact of mitochondrial dysregulation on the carcinogenesis of stomach cancer subtypes. Therefore, gene sets collected related to mitochondria and mitochondrial-dependent processes, from the molecular signatures database. Their expression patterns were analyzed in mRNA expression profiles derived from various cohorts of gastric cancer, as well as RNA sequence TCGA stomach adenocarcinoma profiles. In addition, the Pan-Cancer Atlas expression profile is also used for further validation. Z score-based pathway activation scoring showed that gene sets related to mitochondrial dynamics (fission, fusion, and localizations) were significantly activated and involved in the migration and metastasis of diffuse subtype gastric tumors. By contrast, mitochondrial biogenesis and turnover-associated signatures (such as mitochondrial morphogenesis, membrane organization, depolarization, and mitophagy), were significantly enriched in intestinal subtype gastric tumors. These processes might aid in maintaining mitochondrial mass homeostasis, which in turn helps intestinal-type tumor tissues survive under conditions of nutritional deficiency and/or hypoxia. Results from a single-cell RNA sequence analysis confirmed this dysregulation in gastric cancers. Furthermore, receiver operating characteristic curves showed that diffuse subtype-specific mitochondrial dynamics genes (DNM1L, MFF, FIS1, and OPA1) and intestinal subtype-specific mitochondrial biogenesis and turnover genes (ATP5C1, OXA1L, TIMM10, and PINK1) exhibited a significantly greater degree of sensitivity and specificity in the corresponding subtype of gastric tumors. Finally, overall survival plot studies showed a correlation between the expression of these genes with survival in patients with gastric tumors. The current study concludes that mitochondrial dysregulation might have dual carcinogenic roles in the pathogenesis of diffuse and intestinal subtype gastric tumors. This study should be helpful for the development of targeted treatments for gastric cancer.

RNA interference (RNAi)-based gene silencing has emerged as a potent method for regulating gene expression, with applications spanning biology, medicine, and biotechnology. RNAi exploits natural cellular machinery to selectively suppress target gene expression through the targeted degradation of mRNA based on its specific sequence. MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are two examples of tiny RNA molecules that are introduced during this process; they direct the silencing complex induced by RNA (RISC) in response to complementary mRNA and repress its translation. Several biological functions, including cellular homeostasis maintenance and developmental regulation against viral infections and transposable elements, depend heavily on RNAi-mediated gene silencing. In research, RNAi has revolutionized functional genomics by enabling high-throughput analysis of gene functions and regulatory networks. Moreover, RNAi-based screening approaches have facilitated the discovery of novel drug targets and therapeutic agents. In medicine, RNAi shows potential for addressing genetic disorders, viral infections, cancer, and other diseases by providing a means for precise and targeted intervention. Nevertheless, issues with delivery, specificity, immunogenicity, and safety impede the clinical translation of RNAi-based treatments. RNAi has shown great promise in biotechnology and agriculture for bioproduction, crop improvement, and pest management. Despite these challenges, the rapid advancement of RNAi research and technology holds immense potential to further our understanding of gene regulation and revolutionize therapeutic interventions. An overview of the relevance and uses of RNAi in gene silencing is given in this review, emphasizing the role it will play in directing future biological and medical research.

Mitochondrial dysfunction originating from genetic alterations may play a role in mental illnesses. This study was designed to investigate mitochondrial ND1 mutations associated with schizophrenia and reveal the mRNA expression levels of HSP60 and HSP70. ND1 mutations in 40 patients with schizophrenia were detected by Sanger sequencing. HSP60 and HSP70 mRNA expression levels of patients and healthy controls were evaluated by real-time PCR. Gene expression analysis was conducted using the 2^−∆∆Ct method. The ND1 mutation frequency was 19/40 among the patients. Frequencies of T4216C (n = 8) and A3480G (n = 4) were higher than other mutations. HSP60 expression was higher (p = 0.0145), while HSP70 expression was lower (p = 0.0254) in patients than healthy controls. Carriers of ND1 mutations had lower levels of HSP60 and HSP70 expression than patients who did not carry those mutations (p = 0.1270 and p = 0.6451, respectively). Patients with schizophrenia carrying divergent ND1 mutations showed different expression patterns of HSP60 and HSP70 (p = 0.0434 and p = 0.0969, respectively). In conclusion, patients with schizophrenia had a high frequency of ND1 mutations. Identifying ND1 mutations and analyzing expression levels of HSP60 and HSP70 may contribute to discovering potential molecular markers for diagnosing schizophrenia.

The article titled “DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair” was published in August 2024 in the Proceedings of the National Academy of Sciences (PNAS) by Tang et al. It presents significant advancements in understanding the mechanism of the DNA damage response (DDR), specifically in the context of BRCA1-mediated DNA repair. The authors discovered a novel role of DOT1L, a histone methyltransferase, in facilitating the recruitment of the BRCA1-A complex to DNA damage sites through the methylation of RAP80. This finding has profound implications for the development of new therapeutic strategies, particularly in overcoming resistance to radiotherapy in cancer treatment.