bims-exocan 2023-06-04 papers

Issue of 2023–06–04
three papers selected by
Muhammad Rizwan, COMSATS University

Cancer Lett. 2023 May 27. pii: S0304-3835(23)00196-9. [Epub ahead of print]566 216245

Exosomal circRNAs in cancer: Implications for therapy resistance and biomarkers.

Zhengjun Lin, Yuqiao Ji, Jian Zhou, Guoqing Li, Yanlin Wu, Weifeng Liu, Zhihong Li, Tang Liu.

Despite the advances in cancer treatment in recent years, the development of resistance to cancer therapy remains the biggest hurdle towards curative cancer treatments. Therefore, investigating the molecular mechanisms underlying cancer therapy resistance is of paramount clinical importance. Circular RNAs (circRNAs), novel members of the noncoding RNA family, are endogenous biomolecules in eukaryotes characterized by a covalently closed loop structure with multiple biological functions. Significantly, circRNAs are abundant and stable in exosomes and can be packaged, secreted and transferred to targeted tumour cells, thereby modulating diverse hallmarks of cancer behaviours, such as proliferation, migration, and immune escape. Notably, a great number of exosomal circRNAs are abnormally expressed during cancer treatment and can mediate cancer therapy resistance through complex mechanisms; therefore, targeting exosomal circRNAs is a promising therapeutic method to reverse therapy resistance. This review aimed to elucidate the mechanisms underlying exosomal circRNAs controlling the resistance of cancer to common therapies, such as chemotherapy, targeted therapy, immunotherapy and radiotherapy, and we also discussed the therapeutic potential of exosomal circRNAs as clinical biomarkers and novel targets in cancer clinical management. We also discussed the prospects and challenges of targeting exosomal circRNAs as a novel therapeutic strategy for reversing cancer therapy resistance.

Keywords: Chemoresistance; Exosomes; Immunotherapy; Radiotherapy; Targeted therapy; circRNAs

DOI: https://doi.org/10.1016/j.canlet.2023.216245

Front Genet. 2023 ;14 1138230

Identification of hsa-miR-619-5p and hsa-miR-4454 in plasma-derived exosomes as a potential biomarker for lung adenocarcinoma.

Linxiang Feng, Zian Feng, Jie Hu, Jiahui Gao, Ang Li, Xiaodong He, Liu Liu, Zuojun Shen.

Introduction: Lung cancer has long been at the forefront of all cancers in terms of incidence and mortality. Lung adenocarcinoma is the most common type of lung cancer, accounting for 40% of all lung cancer types. Exosomes can act as biomarkers of tumors and thus play an important role. Methods: In this article, high-throughput sequencing of miRNAs in plasma exosomes from lung adenocarcinoma patients and healthy individuals was performed to obtain 87 upregulated miRNAs, which were then combined with data from the GSE137140 database uploaded by others for screening. The database included 1566 preoperative lung cancer patients, 180 postoperative patients, and 1774 non-cancerous controls. We overlapped the miRNAs upregulated in the serum of lung cancer patients in the database relative to those of non-cancer controls and post-operative patients with the upregulated miRNAs obtained from our next-generation sequencing to obtain nine miRNAs. Two miRNAs that were not reported as tumor markers in lung cancer, hsa-miR-4454 and hsa-miR-619-5p, were selected from them and then validated by qRT-PCR, and further analysis of miRNAs was performed using bioinformatics. Results: Real-time quantitative PCR showed that the expression levels of hsa-miR-4454 and hsa-miR-619-5p in plasma exosomes of patients with lung adenocarcinoma were significantly up-regulated. The AUC values of hsa-miR-619-5p and hsa-miR-4454 were 0.906 and 0.975, respectively, both greater than 0.5, showing good performance. The target genes of miRNAs were screened by bioinformatics methods, and the regulatory network between miRNAs and lncRNAs and mRNAs was studied. Discussion: Our work demonstrated that hsa-miR-4454 and hsa-miR-619-5p have the potential to be used as biomarkers for the early diagnosis of lung adenocarcinoma.

Keywords: bioinformatics; exosome; lung adenocarcinoma; miRNA; qRT-PCR

DOI: https://doi.org/10.3389/fgene.2023.1138230

Funct Integr Genomics. 2023 May 27. 23(2): 184

Therapeutic and diagnostic applications of exosomal circRNAs in breast cancer.

Mohanraj Gopikrishnan, Hephzibah Cathryn R, Gnanasambandan R, Hossam M Ashour, Gianfranco Pintus, Mohamed Hammad, Manoj Kumar Kashyap, George Priya Doss C, Hatem Zayed.

Circular RNAs (circRNAs) are regulatory elements that are involved in orchestrating gene expression and protein functions and are implicated in various biological processes including cancer. Notably, breast cancer has a significant mortality rate and is one of the most common malignancies in women. CircRNAs have been demonstrated to contribute to the pathogenesis of breast cancer including its initiation, progression, metastasis, and resistance to drugs. By acting as miRNA sponges, circRNAs can indirectly influence gene expression by disrupting miRNA regulation of their target genes, ultimately altering the course of cancer development and progression. Additionally, circRNAs can interact with proteins and modulate their functions including signaling pathways involved in the initiation and development of cancer. Recently, circRNAs can encode peptides that play a role in the pathophysiology of breast cancer and other diseases and their potential as diagnostic biomarkers and therapeutic targets for various cancers including breast cancer. CircRNAs possess biomarkers that differentiate, such as stability, specificity, and sensitivity, and can be detected in several biological specimens such as blood, saliva, and urine. Moreover, circRNAs play an important role in various cellular processes including cell proliferation, differentiation, and apoptosis, all of which are integral factors in the development and progression of cancer. This review synthesizes the functions of circRNAs in breast cancer, scrutinizing their contributions to the onset and evolution of the disease through their interactions with exosomes and cancer-related intracellular pathways. It also delves into the potential use of circRNA as a biomarker and therapeutic target against breast cancer. It discusses various databases and online tools that offer crucial circRNA information and regulatory networks. Lastly, the challenges and prospects of utilizing circRNAs in clinical settings associated with breast cancer are explored.

Keywords: Breast cancer; Exosomal circRNAs; Tumor-suppressive circRNAs; circRNA; circRNA biomarkers; miRNA sponges

DOI: https://doi.org/10.1007/s10142-023-01083-3