Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.
R-loops are three-stranded nucleic acid structures composed of an RNA–DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.
15 June 2024 in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
We previously reported that integrin alpha 7 (ITGA7) was downregulated in colorectal cancer (CRC) tissues and CRC cell lines and that the lower expression of ITGA7 in CRC tissues was correlated with distant metastasis, suggesting that ITGA7 may function as a suppressor in CRC. The present research was conducted to further investigate the role and mechanisms of ITGA7 in CRC progression. First, bisulfite modification and genomic sequencing (BSP) results showed that the methylation rate of ITGA7 promoter was higher in 10 CRC tissues than in the matched normal tissues. Additionally, 5-Aza-CdR treatment increased ITGA7 expression in CRC cells. Gain-of-function assays revealed the inhibitory role of ITGA7 in CRC cell proliferation and migration. Mechanistically, RNA sequencing, RT-qPCR, and cytoplasm and nuclear separation and rescue assays indicated that knockdown of ITGA7 activated the transcription of MMP9, SETD7, and ADAM15 by enhancing the nuclear translocation of NF-κB. Moreover, CoIP and Western blot suggested a mechanistic model in which ITGA7 binds to CKAP4 to block the interaction of CKAP4 and PI3K p85α and thereby suppress the PI3K/AKT/NF-κB pathway. Accordingly, the current study suggests that ITGA7 functions as a suppressor in CRC progression and that its expression is controlled by promoter methylation.
Metastasis remains a major cause of morbidity and mortality in patients with malignant tumors. The pre-metastatic niche is a prerequisite for distant metastasis driven by primary tumors. Circular RNAs (circRNAs), a class of single-stranded closed non-coding RNAs, exhibit high stability, evolutionary conservation, and cell-type specificity. Exosomes, as natural carriers of circRNAs, mediate intercellular communication and contribute to the formation of the pre-metastatic niche; however, the mechanisms by which they do so remain incompletely understood. This review summarizes the biological characteristics and functions of exosomal circRNAs and outlines the molecular pathways through which they shape the tumor pre-metastatic microenvironment, with emphasis on immunosuppression, vascular permeability, extracellular matrix remodeling, and lymphangiogenesis. This is the first review to focus on the functional roles and molecular mechanisms of exosomal circRNAs in pre-metastatic niche regulation, providing a basis for the development of therapeutic strategies targeting metastatic progression.
Objective. To investigate the relationship between polymorphism of FOXA1 gene rs12894364 and rs7144658 and susceptibility to gastric cancer. Methods. A case-control study was conducted to select 577 cases of primary gastric cancer and 678 cases of normal control. We extracted whole blood genomic DNA and amplified the target gene fragment by PCR. The genotyping and allele was tested through a snapshot method. Results. There was no significant difference in the frequency distribution of genotype between the case group and control group ( ). Stratified analyses showed the SNPs were not correlated with the susceptibility of GC according to different age, gender, cigarette smoking, and alcohol drinking status. Conclusion. There is no significant correlation between the polymorphisms of FOXA1 gene rs12894364 and rs7144658 and the risk of gastric cancer.