Lung cancer ranks at the top in both incidence and mortality among malignant tumors worldwide. In China, the incidence and mortality of lung cancer are the highest among all malignant tumors. Due to the lack of obvious symptoms in early-stage lung cancer, it is difficult to arouse patients’ vigilance, leading to many patients being diagnosed at an advanced stage, thus missing the best opportunity for treatment. MicroRNAs are a class of single-stranded small RNAs in cells that regulate gene expression in eukaryotes and play a crucial role in the occurrence and development of lung cancer. They have become a frontier and a hot topic in the field of lung cancer research. This article aims to comprehensively review the important position of MicroRNAs in lung cancer research and explore their potential application value as biomarkers in common lung cancers.
References
[1]
Travis, W.D., Brambilla, E., Burke, A.P., Marx, A. and Nicholson, A.G. (2015) Introduction to the 2015 World Health Organization Classification of Tumors of the Lung, Pleura, Thymus, and Heart. Journal of Thoracic Oncology, 10, 1240-1242. https://doi.org/10.1097/jto.0000000000000663
[2]
Allemani, C., Matsuda, T., Di Carlo, V., Harewood, R., Matz, M., Nikšić, M., et al. (2018) Global Surveillance of Trends in Cancer Survival 2000-14 (CONCORD-3): Analysis of Individual Records for 37 513 025 Patients Diagnosed with One of 18 Cancers from 322 Population-Based Registries in 71 Countries. The Lancet, 391, 1023-1075. https://doi.org/10.1016/s0140-6736(17)33326-3
[3]
Biedler, J.L. and Riehm, H. (1970) Cellular Resistance to Actinomycin D in Chinese Hamster Cells in Vitro: Cross-Resistance, Radioautographic, and Cytogenetic Studies. Cancer Research, 30, 1174-1184.
[4]
Fang, C.L. and Guo, L.L. (2014) Progress in the Study of miRNA Regulation of Chemo-Resistance in Lung Cancer. Chinese Journal of Cancer Prevention and Treatment, 21, 72-76. https://doi.org/10.3969/j.issn.1673-5269.2014.01.017
[5]
Oncology Society of Chinese Medical Association (2021) [Oncology Society of Chinese Medical Association Guideline for Clinical Diagnosis and Treatment of Lung Cancer (2021 Edition)]. Chinese Journal of Oncology, 43, 591-621. https://doi.org/10.3760/cma.j.cn112152-20210207-00118
[6]
Barad, O., Meiri, E., Avniel, A., Aharonov, R., Barzilai, A., Bentwich, I., et al. (2004) MicroRNA Expression Detected by Oligonucleotide Microarrays: System Establishment and Expression Profiling in Human Tissues. Genome Research, 14, 2486-2494. https://doi.org/10.1101/gr.2845604
[7]
Naeli, P., Winter, T., Hackett, A.P., Alboushi, L. and Jafarnejad, S.M. (2022) The Intricate Balance between MicroRNA-Induced mRNA Decay and Translational Repression. The FEBS Journal, 290, 2508-2524. https://doi.org/10.1111/febs.16422
[8]
Zhang, J., Li, S., Li, L., Li, M., Guo, C., Yao, J., et al. (2015) Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function. Genomics, Proteomics & Bioinformatics, 13, 17-24. https://doi.org/10.1016/j.gpb.2015.02.001
[9]
Bethke, A., Fielenbach, N., Wang, Z., et al. (2009) Nuclear Hormone Receptor Regulation of MicroRNAs Controls Developmental Progression. Science, 324, 95-98.
[10]
Zhu, L., Sun, H., Wang, S., Huang, S., Zheng, Y., Wang, C., et al. (2020) Isolation and Characterization of Exosomes for Cancer Research. Journal of Hematology & Oncology, 13, Article No. 152. https://doi.org/10.1186/s13045-020-00987-y
[11]
Roundtree, I.A. and He, C. (2016) RNA Epigenetics—Chemical Messages for Posttranscriptional Gene Regulation. Current Opinion in Chemical Biology, 30, 46-51. https://doi.org/10.1016/j.cbpa.2015.10.024
[12]
Sonneveld, S., Verhagen, B.M.P. and Tanenbaum, M.E. (2020) Heterogeneity in mRNA Translation. Trends in Cell Biology, 30, 606-618. https://doi.org/10.1016/j.tcb.2020.04.008
[13]
Fabian, M.R. and Sonenberg, N. (2012) The Mechanics of Mirna-Mediated Gene Silencing: A Look under the Hood of miRISC. Nature Structural & Molecular Biology, 19, 586-593. https://doi.org/10.1038/nsmb.2296
[14]
Thompson, J.R., Zhu, J., Kilari, D. and Wang, L. (2016) Applications of Extracellular RNAs in Oncology. Molecular Diagnosis & Therapy, 21, 1-11. https://doi.org/10.1007/s40291-016-0239-7
[15]
Fabian, M.R., Sonenberg, N. and Filipowicz, W. (2010) Regulation of mRNA Translation and Stability by microRNAs. Annual Review of Biochemistry, 79, 351-379.
[16]
Shademan, B., Karamad, V., Nourazarian, A., Masjedi, S., Isazadeh, A., Sogutlu, F., et al. (2022) MicroRNAs as Targets for Cancer Diagnosis: Interests and Limitations. Advanced Pharmaceutical Bulletin, 13, 435-445. https://doi.org/10.34172/apb.2023.047
[17]
Wang, K., Zhang, S., Weber, J., Baxter, D. and Galas, D.J. (2010) Export of MicroRNAs and MicroRNA-Protective Protein by Mammalian Cells. Nucleic Acids Research, 38, 7248-7259. https://doi.org/10.1093/nar/gkq601
[18]
Xu, L., Yang, B. and Ai, J. (2013) MicroRNA Transport: A New Way in Cell Communication. Journal of Cellular Physiology, 228, 1713-1719. https://doi.org/10.1002/jcp.24344
[19]
Nag, S., Goswami, B., Das Mandal, S. and Ray, P.S. (2022) Cooperation and Competition by RNA-Binding Proteins in Cancer. Seminars in Cancer Biology, 86, 286-297. https://doi.org/10.1016/j.semcancer.2022.02.023
[20]
Ali Syeda, Z., Langden, S.S.S., Munkhzul, C., Lee, M. and Song, S.J. (2020) Regulatory Mechanism of MicroRNA Expression in Cancer. International Journal of Molecular Sciences, 21, 1723. https://doi.org/10.3390/ijms21051723
[21]
Kim, T. and Croce, C.M. (2023) MicroRNA: Trends in Clinical Trials of Cancer Diagnosis and Therapy Strategies. Experimental & Molecular Medicine, 55, 1314-1321. https://doi.org/10.1038/s12276-023-01050-9
[22]
Shah, V. and Shah, J. (2020) Recent Trends in Targeting miRNAs for Cancer Therapy. Journal of Pharmacy and Pharmacology, 72, 1732-1749. https://doi.org/10.1111/jphp.13351
[23]
Reinhart, B.J., Slack, F.J., Basson, M., Pasquinelli, A.E., Bettinger, J.C., Rougvie, A.E., et al. (2000) The 21-Nucleotide Let-7 RNA Regulates Developmental Timing in Caenorhabditis Elegans. Nature, 403, 901-906. https://doi.org/10.1038/35002607
[24]
Brennecke, J., Hipfner, D.R., Stark, A., Russell, R.B. and Cohen, S.M. (2003) Bantam Encodes a Developmentally Regulated MicroRNA That Controls Cell Proliferation and Regulates the Proapoptotic Gene Hid in Drosophila. Cell, 113, 25-36. https://doi.org/10.1016/s0092-8674(03)00231-9
[25]
Xu, P., Vernooy, S.Y., Guo, M. and Hay, B.A. (2003) The Drosophila MicroRNA Mir-14 Suppresses Cell Death and Is Required for Normal Fat Metabolism. Current Biology, 13, 790-795. https://doi.org/10.1016/s0960-9822(03)00250-1
[26]
Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., et al. (2005) miR-15 and miR-16 Induce Apoptosis by Targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America, 102, 13944-13949. https://doi.org/10.1073/pnas.0506654102
[27]
Mitchell, P.S., Parkin, R.K., Kroh, E.M., Fritz, B.R., Wyman, S.K., Pogosova-Agadjanyan, E.L., et al. (2008) Circulating MicroRNAs as Stable Blood-Based Markers for Cancer Detection. Proceedings of the National Academy of Sciences of the United States of America, 105, 10513-10518. https://doi.org/10.1073/pnas.0804549105
[28]
Kavitha, N., Vijayarathna, S., Jothy, S.L., Oon, C.E., Chen, Y., Kanwar, J.R., et al. (2014) MicroRNAs: Biogenesis, Roles for Carcinogenesis and as Potential Biomarkers for Cancer Diagnosis and Prognosis. Asian Pacific Journal of Cancer Prevention, 15, 7489-7497. https://doi.org/10.7314/apjcp.2014.15.18.7489
[29]
Gao, S., Guo, W., Liu, T., Liang, N., Ma, Q., Gao, Y., et al. (2021) Plasma Extracellular Vesicle MicroRNA Profiling and the Identification of a Diagnostic Signature for Stage I Lung Adenocarcinoma. Cancer Science, 113, 648-659. https://doi.org/10.1111/cas.15222
[30]
Wang, W.D., Pei, Z.H., Xi, X.X., et al. (2021) Mining of miR-21 Target Genes in Lung Cancer Patients and Its Expression in Serum and Diagnostic Value. Chinese Journal of Immunology, 37, 4411-4421.
[31]
Wu, J., Feng, Z., Wang, R., Li, A., Wang, H., He, X., et al. (2022) Integration of Bioinformatics Analysis and Experimental Validation Identifies Plasma Exosomal miR-103b/877‐5p/29c‐5p as Diagnostic Biomarkers for Early Lung Adenocarcinoma. Cancer Medicine, 11, 4411-4421. https://doi.org/10.1002/cam4.4788
[32]
Li, X., Qin, M., Huang, J., Ma, J. and Hu, X. (2019) Clinical Significance of miRNA-1 and Its Potential Target Gene Network in Lung Squamous Cell Carcinoma. Molecular Medicine Reports, 19, 5063-5078. https://doi.org/10.3892/mmr.2019.10171
[33]
Chen, S., Lu, H., Chen, G., Yang, J., Huang, W., Wang, X., et al. (2020) Downregulation of miRNA-126-3p Is Associated with Progression of and Poor Prognosis for Lung Squamous Cell Carcinoma. FEBS Open Bio, 10, 1624-1641. https://doi.org/10.1002/2211-5463.12920
[34]
Bica, C., Jurj, A., Harangus, A., et al. (2024) miRNA Patterns in Male LUSC Patients—The 3-Way Mirror: Tissue, Plasma and Exosomes. Translational Oncology, 44, Article ID: 101951.
[35]
Chen, P., Gu, Y., Ma, F., He, R., Li, Z., Zhai, G., et al. (2018) Expression Levels and Cotargets of miRNA-126-3p and miRNA-126-5p in Lung Adenocarcinoma Tissues: Αn Exploration with RT-qPCR, Microarray and Bioinformatic Analyses. Oncology Reports, 41, 939-953. https://doi.org/10.3892/or.2018.6901
[36]
Wang, J., Yao, S., Diao, Y., Geng, Y., Bi, Y. and Liu, G. (2020) miR-15b Enhances the Proliferation and Migration of Lung Adenocarcinoma by Targeting BCL2. Thoracic Cancer, 11, 1396-1405. https://doi.org/10.1111/1759-7714.13382
[37]
Wang, C. and Cheng, B. (2022) MicroRNA miR-3646 Promotes Malignancy of Lung Adenocarcinoma Cells by Suppressing Sorbin and SH3 Domain-Containing Protein 1 via the C-Jun NH2-Terminal Kinase Signaling Pathway. Bioengineered, 13, 4869-4884. https://doi.org/10.1080/21655979.2022.2036889
[38]
Liu, T., Zhu, J., Du, W., Ning, W., Zhang, Y., Zeng, Y., et al. (2020) AKT2 Drives Cancer Progression and Is Negatively Modulated by miR-124 in Human Lung Adenocarcinoma. Respiratory Research, 21, Article No. 227. https://doi.org/10.1186/s12931-020-01491-0
[39]
Bu, L., Tian, Y., Wen, H., Jia, W. and Yang, S. (2020) miR-195-5p Exerts Tumor-Suppressive Functions in Human Lung Cancer Cells through Targeting TrxR2. Acta Biochimica et Biophysica Sinica, 53, 189-200. https://doi.org/10.1093/abbs/gmaa159
[40]
Yuan, C., Bai, R., Gao, Y., Jiang, X., Li, S., Sun, W., et al. (2021) Effects of Microrna‐195-5p on Biological Behaviors and Radiosensitivity of Lung Adenocarcinoma Cells via Targeting HOXA10. Oxidative Medicine and Cellular Longevity, 2021, Article ID: 4522210. https://doi.org/10.1155/2021/4522210
[41]
Song, Y., Kelava, L., Zhang, L. and Kiss, I. (2022) Microarray Data Analysis to Identify miRNA Biomarkers and Construct the lncRNA-miRNA-mRNA Network in Lung Adenocarcinoma. Medicine, 101, e30393. https://doi.org/10.1097/md.0000000000030393
[42]
Guo, L., Li, B., Yang, J., Shen, J., Ji, J. and Miao, M. (2020) Fibroblast-Derived Exosomal microRNA-369 Potentiates Migration and Invasion of Lung Squamous Cell Carcinoma Cells via NF1-Mediated MAPK Signaling Pathway. International Journal of Molecular Medicine, 46, 595-608. https://doi.org/10.3892/ijmm.2020.4614
[43]
Chen, T., Zheng, Q., Gao, F., Yang, T., Ren, H., Li, Y., et al. (2021) MicroRNA-665 Facilitates Cell Proliferation and Represses Apoptosis through Modulating Wnt5a/β-Catenin and Caspase-3 Signaling Pathways by Targeting TRIM8 in LUSC. Cancer Cell International, 21, Article No. 215. https://doi.org/10.1186/s12935-021-01913-z
[44]
Gan, J., Zhang, Y., Liu, S., Mu, G., Zhao, J., Jiang, W., et al. (2023) MicroRNA-375 Restrains the Progression of Lung Squamous Cell Carcinoma by Modulating the ERK Pathway via UBE3A-Mediated DUSP1 Degradation. Cell Death Discovery, 9, Article No. 199. https://doi.org/10.1038/s41420-023-01499-7
[45]
Hu, J., Xiang, X., Guan, W., Lou, W., He, J., Chen, J., et al. (2021) MiR-497-5p Down-Regulates CDCA4 to Restrains Lung Squamous Cell Carcinoma Progression. Journal of Cardiothoracic Surgery, 16, Article No. 330. https://doi.org/10.1186/s13019-021-01698-2
[46]
Shan, X., Zhang, C., Li, C., Fan, X., Song, G., Zhu, J., et al. (2023) MiR-338-3p Acts as a Tumor Suppressor in Lung Squamous Cell Carcinoma by Targeting FGFR2/FRS2. Cancer Pathogenesis and Therapy, 1, 87-97. https://doi.org/10.1016/j.cpt.2022.12.004
[47]
Lone, W., Bouska, A., Sharma, S., Amador, C., Saumyaranjan, M., Herek, T.A., et al. (2021) Genome-Wide miRNA Expression Profiling of Molecular Subgroups of Peripheral T-Cell Lymphoma. Clinical Cancer Research, 27, 6039-6053. https://doi.org/10.1158/1078-0432.ccr-21-0573
[48]
Wei, S., Peng, L., Yang, J., Sang, H., Jin, D., Li, X., et al. (2020) Exosomal Transfer of miR-15b-3p Enhances Tumorigenesis and Malignant Transformation through the DYNLT1/Caspase-3/Caspase-9 Signaling Pathway in Gastric Cancer. Journal of Experimental & Clinical Cancer Research, 39, Article No. 32. https://doi.org/10.1186/s13046-019-1511-6
[49]
Wu, B., Liu, G., Jin, Y., Yang, T., Zhang, D., Ding, L., et al. (2020) MiR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2. Frontiers in Oncology, 10, Article 108. https://doi.org/10.3389/fonc.2020.00108
[50]
Zhang, K., Zhao, S., Wang, Q., Yang, H., Zhu, J. and Ma, R. (2015) Identification of MicroRNAs in Nipple Discharge as Potential Diagnostic Biomarkers for Breast Cancer. Annals of Surgical Oncology, 22, 536-544. https://doi.org/10.1245/s10434-015-4586-0
[51]
Song, B., Xu, L., Jiang, K. and Cheng, F. (2023) MiR-124-3p Inhibits Tumor Progression in Prostate Cancer by Targeting EZH2. Functional & Integrative Genomics, 23, Article No. 80. https://doi.org/10.1007/s10142-023-00991-8
[52]
Yan, G., Li, Y., Zhan, L., et al. (2019) Decreased miR-124-3p Promoted Breast Cancer Proliferation and Metastasis by Targeting MGAT5. American Journal of Cancer Research, 9, 585-596.
[53]
Moorthy, R.K., Srinivasan, C., Kannan, M. and Arockiam, A.J.V. (2023) Deregulation of miR-375 Inhibits HOXA5 and Promotes Migration, Invasion, and Cell Proliferation in Breast Cancer. Applied Biochemistry and Biotechnology, 195, 4503-4523. https://doi.org/10.1007/s12010-023-04375-3
[54]
Zhao, X., Hu, J., Tang, J., Yi, W., Zhang, M., Deng, R., et al. (2019) miR-665 Expression Predicts Poor Survival and Promotes Tumor Metastasis by Targeting NR4A3 in Breast Cancer. Cell Death & Disease, 10, Article No. 479. https://doi.org/10.1038/s41419-019-1705-z
[55]
Wu, K., Zhang, C., Zhang, C., Pei, J. and Dai, D. (2020) miR-665 Suppresses the Epithelial-Mesenchymal Transition and Progression of Gastric Cancer by Targeting CRIM1. Cancer Management and Research, 12, 3489-3501. https://doi.org/10.2147/cmar.s241795
[56]
Gharib, E., Nasri Nasrabadi, P. and Reza Zali, M. (2020) miR-497-5p Mediates Starvation-Induced Death in Colon Cancer Cells by Targeting Acyl-CoA Synthetase-5 and Modulation of Lipid Metabolism. Journal of Cellular Physiology, 235, 5570-5589. https://doi.org/10.1002/jcp.29488
