The Role of Circular RNAs in the Drug Resistance of Cancers

Cancer is a major threat to human health and longevity. Chemotherapy is an effective approach to inhibit cancer cell proliferation, but a growing number of cancer patients are prone to develop resistance to various chemotherapeutics, including platinum, paclitaxel, adriamycin, and 5-fluorouracil, among others. Significant progress has been made in the research and development of chemotherapeutic drugs over the last few decades, including targeted therapy drugs and immune checkpoint inhibitors; however, drug resistance still severely limits the application and efficacy of these drugs in cancer treatment. Recently, emerging studies have emphasized the role of circular RNAs (circRNAs) in the proliferation, migration, invasion, and especially chemoresistance of cancer cells by regulating the expression of related miRNAs and targeted genes. In this review, we comprehensively summarized the potential roles and mechanisms of circRNAs in cancer drug resistance including the efflux of drugs, apoptosis, intervention with the TME (tumor microenvironment), autophagy, and dysfunction of DNA damage repair, among others. Furthermore, we highlighted the potential value of circRNAs as new therapeutic targets and prognostic biomarkers for cancer.

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Novel Implications of MicroRNAs, Long Non-coding RNAs and Circular RNAs in Drug Resistance of Esophageal Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.764313 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ling Wei ◽

Jujie Sun ◽

Nasha Zhang ◽

Yue Shen ◽

Teng Wang ◽

...

Keyword(s):

Drug Resistance ◽

Esophageal Cancer ◽

Checkpoint Inhibitors ◽

Cancer Drug ◽

Circular Rnas ◽

Cancer Drug Resistance ◽

Novel Biomarkers ◽

Non Coding Rnas ◽

Underlying Mechanisms ◽

Poor Outcomes

Esophageal cancer is the eighth most common malignancy and the sixth leading cause of cancer-related deaths worldwide. Chemotherapy based on platinum drugs, 5-fluorouracil, adriamycin, paclitaxel, gemcitabine, and vinorelbine, as well as targeted treatment and immunotherapy with immune checkpoint inhibitors improved the prognosis in a portion of patients with advanced esophageal cancer. Unfortunately, a number of esophageal cancer patients develop drug resistance, resulting in poor outcomes. Multiple mechanisms contributing to drug resistance of esophageal cancer have been reported. Notably, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have been identified to play crucial roles in modulating esophageal cancer drug resistance. In the present review, we highlight the underlying mechanisms how miRNAs, lncRNAs, and circRNAs impact the drug resistance of esophageal cancer. Several miRNAs, lncRNAs, and circRNAs may have potential clinical implications as novel biomarkers and therapeutic targets for esophageal cancer.

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Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00300-w ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Huibin Song ◽

Dongcheng Liu ◽

Shaowei Dong ◽

Leli Zeng ◽

Zhuoxun Wu ◽

...

Keyword(s):

Drug Resistance ◽

Posttranslational Modification ◽

Drug Target ◽

Epithelial Mesenchymal Transition ◽

Cancer Drug ◽

Chemotherapeutic Drugs ◽

Mesenchymal Transition ◽

Therapeutic Implications ◽

Cancer Drug Resistance ◽

Damage Repair

Abstract Drug resistance is a major hurdle in cancer treatment and a key cause of poor prognosis. Epitranscriptomics and epiproteomics are crucial in cell proliferation, migration, invasion, and epithelial–mesenchymal transition. In recent years, epitranscriptomic and epiproteomic modification has been investigated on their roles in overcoming drug resistance. In this review article, we summarized the recent progress in overcoming cancer drug resistance in three novel aspects: (i) mRNA modification, which includes alternative splicing, A-to-I modification and mRNA methylation; (ii) noncoding RNAs modification, which involves miRNAs, lncRNAs, and circRNAs; and (iii) posttranslational modification on molecules encompasses drug inactivation/efflux, drug target modifications, DNA damage repair, cell death resistance, EMT, and metastasis. In addition, we discussed the therapeutic implications of targeting some classical chemotherapeutic drugs such as cisplatin, 5-fluorouridine, and gefitinib via these modifications. Taken together, this review highlights the importance of epitranscriptomic and epiproteomic modification in cancer drug resistance and provides new insights on potential therapeutic targets to reverse cancer drug resistance.

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Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives

EMBO Molecular Medicine ◽

10.1002/emmm.201101131 ◽

2012 ◽

Vol 4 (8) ◽

pp. 675-684 ◽

Cited By ~ 134

Author(s):

Nicholas A. Saunders ◽

Fiona Simpson ◽

Erik W. Thompson ◽

Michelle M. Hill ◽

Liliana Endo‐Munoz ◽

...

Keyword(s):

Drug Resistance ◽

Cancer Drug ◽

Cancer Drug Resistance ◽

Intratumoural Heterogeneity

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Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance

Biochemical Pharmacology ◽

10.1016/j.bcp.2012.01.002 ◽

2012 ◽

Vol 83 (8) ◽

pp. 1084-1103 ◽

Cited By ~ 229

Author(s):

Karthika Natarajan ◽

Yi Xie ◽

Maria R. Baer ◽

Douglas D. Ross

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Breast Cancer Resistance Protein ◽

Cancer Drug ◽

Cancer Resistance ◽

Cancer Drug Resistance ◽

Resistance Protein

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The role of photodynamic therapy in overcoming cancer drug resistance

Photochemical & Photobiological Sciences ◽

10.1039/c4pp00495g ◽

2015 ◽

Vol 14 (8) ◽

pp. 1476-1491 ◽

Cited By ~ 122

Author(s):

Bryan Q. Spring ◽

Imran Rizvi ◽

Nan Xu ◽

Tayyaba Hasan

Keyword(s):

Drug Resistance ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Cancer Drug ◽

Cancer Drug Resistance

This perspective highlights unique mechanisms of photodynamic therapy (PDT) that can be utilized to overcome classical drug resistance and re-sensitize resistant cancer cells for standard therapies.

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