Effects of microRNA on the growth and targeted therapy response on lung cancer

Abstract

Lung cancer represents a significant public health concern worldwide. Lung cancer typically receives a diagnosis at a late stage, leading to a generally unfavourable prognosis. Additionally, traditional treatments frequently fail in cases of metastatic lung cancer. However, targeted therapy has advanced considerably in the management of lung cancer, and overcoming drug resistance has emerged as a significant hurdle in achieving optimal treatment outcomes. As a result, there has been a new trend toward precision therapy for lung cancer based on changes at the molecular and genetic levels. On the other hand, for lung cancer, early diagnosis plays a crucial role in treatment and prognosis. Based on existing knowledge, we strongly believe that it is imperative to promptly identify innovative biomarkers. The emergence of microRNAs (miRNAs) provides new ideas. The expression profiles of miRNAs have been investigated using noninvasive blood samples to explore the regulatory mechanisms played by miRNAs during the progression and targeted therapy resistance of lung cancer. Due to the complexity of miRNA profiles, they may play the role of tumour suppressors or oncogenes. However, specific regulatory mechanisms are still a huge topic to be explored. In this Review, we summarize the latest research that has shed light on the potential regulatory mechanisms of miRNAs in driving lung cancer progression, their value for clinical application as biomarkers and their role in targeted therapy resistance.

Keywords

biomarkers / drug resistance / lung cancer / miRNA / targeted therapy

References

[1] LiY, YanB, HeS. Advances and challenges in the treatment of lung cancer. Biomed Pharmacother. 2023;169:115891.

[2] XiaC, DongX, LiH, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022;135(5):584-590.

[3] TorreLA, SiegelRL, JemalA. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1-19.

[4] PeiQ, LuoY, ChenY, et al. Artificial intelligence in clinical applications for lung cancer: diagnosis, treatment and prognosis. Clin Chem Lab Med. 2022;60(12):1974-1983.

[5] PirkerR. Conquering lung cancer: current status and prospects for the future. Pulmonology. 2020;26(5):283-290.

[6] NooreldeenR, BachH. Current and future development in lung cancer diagnosis. Int J Mol Sci. 2021;22(16):8661.

[7] LiMY, LiuLZ, DongM. Progress on pivotal role and application of exosome in lung cancer carcinogenesis, diagnosis, therapy and prognosis. Mol Cancer. 2021;20(1):22.

[8] AlexanderM, KimSY, ChengH. Update 2020: management of non-small cell lung cancer. Lung. 2020;198(6):897-907.

[9] KilikeviciusA, Meister G, CoreyDR. Reexamining assumptions about miRNA-guided gene silencing. Nucleic Acids Res. 2022;50(2):617-634.

[10] FrydrychowiczM, KuszelŁ, DworackiG, et al. MicroRNA in lung cancer-a novel potential way for early diagnosis and therapy. J Appl Genet. 2023;64(3):459-477.

[11] MenonA, Abd-Aziz N, KhalidK, et al. miRNA: a promising therapeutic target in cancer. Int J Mol Sci. 2022;23(19):11502.

[12] HeB, ZhaoZ, CaiQ, et al. miRNA-based biomarkers, therapies, and resistance in cancer. Int J Biol Sci. 2020;16(14):2628-2647.

[13] IqbalMA, AroraS, PrakasamG, et al. MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance. Mol Aspects Med. 2019;70:3-20.

[14] DuX, ZhangJ, WangJ, et al. Role of miRNA in lung cancer-potential biomarkers and therapies. Curr Pharm Des. 2018;23(39):5997-6010.

[15] HussenBM, Hidayat HJ, SalihiA, et al. MicroRNA: a signature for cancer progression. Biomed Pharmacother. 2021;138:111528.

[16] DienerC, KellerA, MeeseE. Emerging concepts of miRNA therapeutics: from cells to clinic. Trends Genet. 2022;38(6):613-626.

[17] UsóM, Jantus-Lewintre E, SireraR, et al. miRNA detection methods and clinical implications in lung cancer. Future Oncol. 2014;10(14):2279-2292.

[18] WuM, WangG, TianW, et al. miRNA-based therapeutics for lung cancer. Curr Pharm Des. 2018;23(39):5989-5996.

[19] LiG, FangJ, WangY, et al. miRNA-based therapeutic strategy in lung cancer. Curr Pharm Des. 2018;23(39):6011-6018.

[20] LiangG, MengW, HuangX, et al. miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumour progression in non-small cell lung cancer. Proc Natl Acad Sci U S A. 2020;117(8):4347-4357.

[21] WangW, HongG, WangS, et al. Tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting growth arrest-specific homeobox gene (GAX). Bioengineered. 2021;12(1):821-831.

[22] BaiJ, ShiZ, WangS, et al. MiR-21 and let-7 cooperation in the regulation of lung cancer. Front Oncol. 2022;12:950043.

[23] ZhouJS, YangZS, ChengSY, et al. miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis. BMC Pulm Med. 2020;20(1):223.

[24] GongJ, ShenY, JiangF, et al. MicroRNA-20a promotes non-small cell lung cancer proliferation by upregulating PD-L1 by targeting PTEN. Oncol Lett. 2022;23(5):148.

[25] TanX, TongL, LiL, et al. Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation. Nat Commun. 2021;12(1):4853.

[26] HashemiS, YariN, Rahimi JamnaniF, et al. The role of miRNA-377 as a tumour suppressor in lung cancer by negative regulation of genes belonging to ErbB signaling pathway. Mol Biol Rep. 2022;49(1):85-95.

[27] NagasakaM, UddinMH, Al-HallakMN, et al. Liquid biopsy for therapy monitoring in early-stage non-small cell lung cancer. Mol Cancer. 2021;20(1):82.

[28] LoberaES, VarelaMA, JimenezRL, et al. miRNA as biomarker in lung cancer. Mol Biol Rep. 2023;50(11):9521-9527.

[29] LotfiE, Kholghi A, GolabF, et al. Circulating miRNAs and lncRNAs serve as biomarkers for early colorectal cancer diagnosis. Pathol Res Pract. 2024;255:155187.

[30] HettaHF, ZahranAM, ShafikEA, et al. Circulating miRNA-21 and miRNA-23a expression signature as potential biomarkers for early detection of non-small-cell lung cancer. Microrna. 2019;8(3):206-215.

[31] AlexandreD, Teixeira B, RicoA, et al. Molecular Beacon for detection miRNA-21 as a biomarker of lung cancer. Int J Mol Sci. 2022;23(6):3330.

[32] ChoWC, WongCF, LiKP, et al. miR-145 as a potential biomarker and therapeutic target in patients with non-small cell lung cancer. Int J Mol Sci. 2023;24(12):10022.

[33] GrendaA, Kuźnar-Kamińska B, KalinkaE, et al. MicroRNA-126 selected with broad-spectrum analysis of microRNAs-a new predictive factor for the effectiveness of immunotherapy or chemoimmunotherapy in advanced NSCLC patients. Front Immunol. 2024;15:1344858.

[34] Abu RousF, SinghiEK, SridharA, et al. Lung cancer treatment advances in 2022. Cancer Invest. 2023;41(1):12-24.

[35] SalgiaR, Pharaon R, MambetsarievI, et al. The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). Cell Rep Med. 2021;2(1):100186.

[36] ZhaoY, GuoS, DengJ, et al. VEGF/VEGFR-targeted therapy and immunotherapy in non-small cell lung cancer: targeting the tumor microenvironment. Int J Biol Sci. 2022;18(9):3845-3858.

[37] WuJ, LinZ. Non-small cell lung cancer targeted therapy: drugs and mechanisms of drug resistance. Int J Mol Sci. 2022;23(23):15056.

[38] HeJ, HuangZ, HanL, et al. Mechanisms and management of 3rd generation EGFR-TKI resistance in advanced non-small cell lung cancer (Review). Int J Oncol. 2021;59(5):90.

[39] LimZF, MaPC. Emerging insights of tumour heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 2019;12(1):134.

[40] WuSG, ShihJY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer. 2018;17(1):38.

[41] LiJW, ZhengG, KayeFJ, et al. PROTAC therapy as a new targeted therapy for lung cancer. Mol Ther. 2023;31(3):647-656.

[42] UsóM, Jantus-Lewintre E, SireraR, BremnesRM. Camps C. miRNA detection methods and clinical implications in lung cancer. Future Oncol. 2014;10(14):2279-2292.

[43] PanG, LiuY, ShangL, Zhou F, YangS. EMT-associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun. 2021;41(3):199-217.

[44] HirschFR, Scagliotti GV, MulshineJL, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389(10066):299-311.

[45] HuangWC, YadavVK, ChengWH, et al. The MEK/ERK/miR-21 signaling is critical in osimertinib resistance in EGFR-mutant non-small cell lung cancer cells. Cancers. 2021;13(23):6005.

[46] GuG, HuC, HuiK, et al. Exosomal miR-136-5p derived from anlotinib-resistant NSCLC cells confers anlotinib resistance in non-small cell lung cancer through targeting PPP2R2A. Int J Nanomedicine. 2021;16:6329-6343.

[47] ChenJ, CuiJD, GuoXT, et al. Increased expression of miR-641 contributes to erlotinib resistance in non-small-cell lung cancer cells by targeting NF1. Cancer Med. 2018;7(4):1394-1403.

[48] GaoY, FanX, LiW, et al. miR-138-5p reverses gefitinib resistance in non-small cell lung cancer cells via negatively regulating G protein-coupled receptor 124. Biochem Biophys Res Commun. 2014;446(1):179-186.

[49] LiuS, JiangZ, XiaoP, et al. Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells. Cancer Sci. 2022;113(1):79-90.

[50] XiongR, SunXX, WuHR, et al. Mechanism research of miR-34a regulates Axl in non-small-cell lung cancer with gefitinib-acquired resistance. Thorac Cancer. 2020;11(1):156-165.

[51] JiaoD, JiangC, ZhuL, et al. miR-1/133a and miR-206/133b clusters overcome HGF induced gefitinib resistance in non-small cell lung cancers with EGFR sensitive mutations. J Drug Target. 2021;29(10):1111-1117.

[52] ChenR, QianZ, XuX, et al. Exosomes-transmitted miR-7 reverses gefitinib resistance by targeting YAP in non-small-cell lung cancer. Pharmacol Res. 2021;165:105442.

[53] YuB, ZhengL, TangH, et al. Cucurbitacin B enhances apoptosis in gefitinib resistant non small cell lung cancer by modulating the miR-17-5p/STAT3 axis. Mol Med Rep. 2021;24(4):710.

[54] WuSG, ChangTH, TsaiMF, et al. miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44. Mol Ther Nucleic Acids. 2023;35(1):102091.

[55] DuW, SunL, LiuT, et al. The miR 625 3p/AXL axis induces non T790M acquired resistance to EGFR TKI via activation of the TGF β/Smad pathway and EMT in EGFR mutant non small cell lung cancer. Oncol Rep. 2020;44(1):185-195.

[56] ZhengY, GuoZ, LiY. Long non-coding RNA prostate cancer-associated transcript 6 inhibited gefitinib sensitivity of non-small cell lung cancer by serving as a competing endogenous RNA of miR-326 to up-regulate interferon-alpha receptor 2. Bioengineered. 2022;13(2):3785-3796.

[57] WangC, DingS, SunB, et al. Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib. Pharmacol Res. 2020;161:105110.

[58] TodenS, GoelA. Non-coding RNAs as liquid biopsy biomarkers in cancer. Br J Cancer. 2022;126(3):351-360.

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2024 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.