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Review
. 2022 Oct 25:13:949566.
doi: 10.3389/fphar.2022.949566. eCollection 2022.

miRNAs in anti-cancer drug resistance of non-small cell lung cancer: Recent advances and future potential

Hang Yan  1   2 , Shengjie Tang  1 , Shoujun Tang  1 , Jun Zhang  1   2 , Haiyang Guo  1   3 , Chao Qin  1   2 , Haiyang Hu  1   2 , Chuan Zhong  1 , Li Yang  1 , Yunhe Zhu  1 , Haining Zhou  1   2   3
Affiliations
Review

miRNAs in anti-cancer drug resistance of non-small cell lung cancer: Recent advances and future potential

Hang Yan et al. Front Pharmacol. .

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Clinical success is suboptimal owing to late diagnosis, limited treatment options, high recurrence rates, and the development of drug resistance. MicroRNAs (miRNAs), a range of small endogenous non-coding RNAs that are 22 nucleotides in length, have emerged as one of the most important players in cancer initiation and progression in recent decades. Current evidence has revealed the pivotal roles of miRNAs in regulating cell proliferation, migration, invasion, and metastasis in NSCLC. Recently, several studies have demonstrated that miRNAs are strongly associated with resistance to anti-cancer drugs, ranging from traditional chemotherapeutic and immunotherapy drugs to anti-vascular drugs, and even during radiotherapy. In this review, we briefly introduce the mechanism of miRNA dysregulation and resistance to anti-tumor therapy in NSCLC, and summarize the role of miRNAs in the malignant process of NSCLC. We then discuss studies of resistance-related miRNAs in chemotherapy, radiotherapy, targeted therapy, immunotherapy, and anti-vascular therapy in NSCLC. Finally, we will explore the application prospects of miRNA, an emerging small molecule, for future anti-tumor therapy. This review is the first to summarize the latest research progress on miRNAs in anti-cancer drug resistance based on drug classification, and to discuss their potential clinical applications.

Keywords: NSCLC; biomarker; drug resistance; miRNA; therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
miRNA biogenesis and action. miRNA genes are transcribed by RNA polymerase II to produce primary miRNA (Pri-miRNA), Pri-miRNA is further processed by Drosha-Dgcr8 in the nucleus to form pre-miRNA, which is then exported to the cytoplasm via Exportin5/Ran GTP. TRBP, and DICER in the cytoplasm further process the pre-miRNA into mature short double strand RNA fragments. One mature miRNA is associated with the Argonaute protein (AGO2) and binds to the 3′UTR of the complementary site target mRNA of RISC leading to translation inhibition while the other strand is degraded.
FIGURE 2
FIGURE 2
Drug resistance in non-small cell lung cancer. The mechanisms of drug resistance in NSCLC are complex and diverse, including ABC transporter activity, anti-apoptosis, autophagy induction, EGFR mutation, EMT promotion, angiogenesis promotion and checkpoint changes. The figure shows the mechanism of miRNA involved in different drug resistance processes of NSCLC. Abbreviations: ABC, ATP-binding cassette; EMT, epithelial–mesenchymal transition; EGFR, epidermal growth factor receptor; VEGF, vascular endothelial growth factor.
See this image and copyright information in PMC

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