Study on the Mechanism of miR-520d-5p and LMO4 in Regulating Thyroid Cancer Progression
Keywords:
thyroid neoplasms, molecular mechanism, molecular markers, oncogene, gene mutation
Abstract
The pathogenesis of thyroid cancer is closely related to environmental factors. Gene mutation and molecular biological changes of thyroid tissue caused by environmental changes are one of the important factors inducing thyroid cancer. Although the molecular mechanism of thyroid cancer is still not fully elucidated, with the development of molecular biology technology, more and more thyroid cancer-specific genetic changes and molecular markers have been excavated. This article systematically summarizes the current research progress of miR-520d-5p and LMO4 in thyroid cancer, and discusses how they participate in the regulation of the biological behavior of tumor cells and potential molecular signaling pathways, so as to provide new theoretical basis and ideas for the precise diagnosis and treatment of thyroid cancer.
References
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[19] Liu, B., Yang, P., Xu, F., et al. (2021). MYBL2-induced PITPNA-AS1 upregulates SIK2 to exert oncogenic function in triple-negative breast cancer through miR-520d-5p and DDX54. Journal of Translational Medicine, 19(1), 333. https://doi.org/10.1186/s12967-021-02956-6
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[25] Ning, W., Qing, D., & Zhang, X. N. (2019). LMO4 promotes the invasion and proliferation of gastric cancer by activating PI3K-Akt-mTOR signaling. American Journal of Translational Research, 11(10), 6534–6543.
[26] Miura, N., Ishihara, Y., Miura, Y., et al. (2019). miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives. BMC Cancer, 19(1), 1–12. https://doi.org/10.1186/s12885-019-5786-y
[27] Deng, K., Wang, Z., Liu, X., et al. (2018). LMO4 mediates trastuzumab resistance in HER2 positive breast cancer cells. American Journal of Cancer Research, 8(4), 594–609.
[28] Dandapani, P. R., Yadav, K. V. B. S. C., Panda, M., et al. (2017). SIRP alpha protein downregulates in human astrocytoma: Presumptive involvement of hsa-miR-520d-5p and hsa-miR-520d-3p. Molecular Neurobiology, 54(10), 8162–8169. https://doi.org/10.1007/s12035-016-0302-8
[29] Zhang, T., Jiang, K., Xu, X., et al. (2017). MicroRNA-520d-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting PTTG1. American Journal of Translational Research, 9(11), 4872–4887.
[30] Ishida, Y., Takahashi, S., Kojima, S., et al. (2016). Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model. BMC Cancer, 16(1), 415. https://doi.org/10.1186/s12885-016-2467-y
[31] Lung Cancer; New lung cancer study findings reported from University Hospital. (2013). Biotech Week.
[32] Zhou, X., Sang, M., Liu, W., et al. (2012). LMO4 inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53. Life Sciences, 91(9–10), 358–363. https://doi.org/10.1016/j.lfs.2012.08.005
[33] Karachaliou, N., Costa, C., Gimenez-Capitan, A., et al. (2012). High mRNA expression of LMO4, a BRCA1 downregulator, correlates with better prognosis in Erlotinib-treated non-small-cell lung cancer (NSCLC) patients (P) with EGFR mutations. Annals of Oncology, 23(S9), ix531. https://doi.org/10.1016/S0923-7534(20)34199-5
[34] Montañez, E. M. M., Scherer, D. D., Li, D. M., et al. (2009). LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progression. Oncogene, 28(41), 3608–3618. https://doi.org/10.1038/onc.2009.221
[35] Yamashita, J., Ozawa, K., Nakanishi, K., et al. (2008). LIM only 4 is overexpressed in late stage pancreas cancer. Molecular Cancer, 7(1), 93. https://doi.org/10.1186/1476-4598-7-93
[36] Wang, N., Kong, K. K. L., Zhang, L., et al. (2007). The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells. Oncogene, 26(44), 6431–6441. https://doi.org/10.1038/sj.onc.1210465
[37] Lu, Z., Lam, S. K., Wang, N., et al. (2006). LMO4 can interact with Smad proteins and modulate transforming growth factor-β signaling in epithelial cells. Oncogene, 25(20), 2920–2930. https://doi.org/10.1038/sj.onc.1209318
[38] Zhang, L., Lam, S. K., Wang, N., et al. (2006). LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells. Oncogene, 25(20), 2920–2930. https://doi.org/10.1038/sj.onc.1209318
[2] Kozłowski, M., Borzyszkowska, D., Golara, A., et al. (2025). The role of microRNA in the prognosis and diagnosis of ovarian cancer. International Journal of Molecular Sciences, 26(7), 3413. https://doi.org/10.3390/ijms26073413
[3] Ma, Z., Mu, R., Zhou, Z., et al. (2025). The mammalian acid chitinase promotes oncogenic properties of thyroid cancer cells through the JAK2/STAT3 pathway. European Thyroid Journal, 2025. https://doi.org/10.1530/ETJ-24-0311
[4] Lu, J., Zhou, X., Zhu, H., et al. (2025). POGZ targeted by LINC01355/miR-27b-3p retards thyroid cancer progression via interplaying with MAD2L2. 3 Biotech, 15(4), 79. https://doi.org/10.1007/s13205-025-04231-7
[5] Zhu, Q., Liu, J., Hu, J., et al. (2025). The epidemiological landscape of thyroid cancer and estimates of overdiagnosis in China: A population-based study. Thyroid: Official Journal of the American Thyroid Association, 2025. https://doi.org/10.1089/thy.2024.0583
[6] Seok, J. H., Choi, Y. J., Lee, H. D., et al. (2024). Atomoxetine suppresses radioresistance in glioblastoma via circATIC/miR-520d-5p/Notch2-Hey1 axis. Cell Communication and Signaling, 22(1), 532. https://doi.org/10.1186/s12964-024-01915-0
[7] Shang, F., Xu, Z., Wang, H., et al. (2024). Elucidating macrophage scavenger receptor 1’s mechanistic contribution as a shared molecular mediator in obesity and thyroid cancer pathogenesis via bioinformatics analysis. Frontiers in Genetics, 151483991. https://doi.org/10.3389/fgene.2024.1483991
[8] Ždralević, M., Radović, A., Raonić, J., et al. (2024). Advances in microRNAs as emerging biomarkers for colorectal cancer early detection and diagnosis. International Journal of Molecular Sciences, 25(20), 11060. https://doi.org/10.3390/ijms252011060
[9] Zhao, W., Wang, W., Zhu, Y., et al. (2024). Molecular mechanisms and clinicopathological characteristics of inhibin βA in thyroid cancer metastasis. International Journal of Molecular Medicine, 54(5). https://doi.org/10.3892/ijmm.2024.5423
[10] Sun, C., & Liao, L. (2024). Research progress of the molecular mechanism of antithyroid cancer activity of Shikonin. Current Molecular Pharmacology, 17(1), 1–8. https://doi.org/10.2174/1874467217666230904104414
[11] Miao, Y., Xiuting, H., Ting, L., et al. (2023). lncRNA GPRC5D-AS1 as a ceRNA inhibits skeletal muscle aging by regulating miR-520d-5p. Aging, 15(23), 13980–13997. https://doi.org/10.18632/aging.205279
[12] Yue, B. H., Zhebin, L., Xin, H., et al. (2022). HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms. Cell Death & Disease, 13(11), 940. https://doi.org/10.1038/s41419-022-05376-6
[13] Mingjiu, C., Zhenkun, X., Jie, D. (2022). Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying miR-655-3p inhibit the development of esophageal cancer by regulating the expression of HIF-1α via a LMO4/HDAC2-dependent mechanism. Cell Biology and Toxicology, 39(4), 1319–1339. https://doi.org/10.1007/s10565-022-09759-5
[14] Jieyun, X., Shijie, Q., Yunmeng, Y., et al. (2022). Delving into the heterogeneity of different breast cancer subtypes and the prognostic models utilizing scRNA-Seq and bulk RNA-Seq. International Journal of Molecular Sciences, 23(17), 9936. https://doi.org/10.3390/ijms23179936
[15] Hery, M. C., Muthusamy, K., Wijayawardana, R. J., et al. (2022). Molecular mechanisms of resistance to kinase inhibitors in thyroid cancers. Endocrine-Related Cancer, 29(11).
[16] Yang, L., Suliman, K., Lin, L., et al. (2021). Molecular mechanisms of thyroid cancer: A competing endogenous RNA (ceRNA) point of view. Biomedicine & Pharmacotherapy, 146, 112251. https://doi.org/10.1016/j.biopha.2021.112251
[17] Baroni, P. P. B. V., Pampolha, V. A. G., Pereira, R. E. G., et al. (2021). Osteopontin expression in thyroid cancer: Deciphering EMT-related molecular mechanisms. Biomedicines, 9(10), 1372. https://doi.org/10.3390/biomedicines9101372
[18] Li, Y., Pan, J., & Liu, M. (2021). Secular trends in the epidemiologic patterns of thyroid cancer in China over three decades: An updated systematic analysis of Global Burden of Disease Study 2019 data. Frontiers in Endocrinology, 12, 707233. https://doi.org/10.3389/fendo.2021.707233
[19] Liu, B., Yang, P., Xu, F., et al. (2021). MYBL2-induced PITPNA-AS1 upregulates SIK2 to exert oncogenic function in triple-negative breast cancer through miR-520d-5p and DDX54. Journal of Translational Medicine, 19(1), 333. https://doi.org/10.1186/s12967-021-02956-6
[20] Miura, N., & Smirnov, V. (2021). Molecular pathogenesis of pediatric thyroid carcinoma. Journal of Radiation Research, 62(S1), i71–i77. https://doi.org/10.1093/jrr/rraa096
[21] Ding, L., Zhang, Z., Zheng, R., et al. (2020). Epidemiology of thyroid cancer: Incidence and mortality in China, 2015. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.01702
[22] Lei, L., Yuan, C., Tang, S., et al. (2020). Circ0058124 aggravates the progression of papillary thyroid carcinoma by activating LMO4 expression via targeting miR-370-3p. Cancer Management and Research, 2020, 9459–9470. https://doi.org/10.2147/CMAR.S271778
[23] Li, J., Zhang, Z., Sun, B., et al. (2020). MiR-520d-5p modulates chondrogenesis and chondrocyte metabolism through targeting HDAC1. Aging, 12. https://doi.org/10.18632/aging.103831
[24] Zhang, L., Liu, F., Fu, Y., et al. (2020). MiR-520d-5p functions as a tumor-suppressor gene in cervical cancer through targeting PTK2. Life Sciences, 254, 117558. https://doi.org/10.1016/j.lfs.2020.117558
[25] Ning, W., Qing, D., & Zhang, X. N. (2019). LMO4 promotes the invasion and proliferation of gastric cancer by activating PI3K-Akt-mTOR signaling. American Journal of Translational Research, 11(10), 6534–6543.
[26] Miura, N., Ishihara, Y., Miura, Y., et al. (2019). miR-520d-5p can reduce the mutations in hepatoma cancer cells and iPSCs-derivatives. BMC Cancer, 19(1), 1–12. https://doi.org/10.1186/s12885-019-5786-y
[27] Deng, K., Wang, Z., Liu, X., et al. (2018). LMO4 mediates trastuzumab resistance in HER2 positive breast cancer cells. American Journal of Cancer Research, 8(4), 594–609.
[28] Dandapani, P. R., Yadav, K. V. B. S. C., Panda, M., et al. (2017). SIRP alpha protein downregulates in human astrocytoma: Presumptive involvement of hsa-miR-520d-5p and hsa-miR-520d-3p. Molecular Neurobiology, 54(10), 8162–8169. https://doi.org/10.1007/s12035-016-0302-8
[29] Zhang, T., Jiang, K., Xu, X., et al. (2017). MicroRNA-520d-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting PTTG1. American Journal of Translational Research, 9(11), 4872–4887.
[30] Ishida, Y., Takahashi, S., Kojima, S., et al. (2016). Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model. BMC Cancer, 16(1), 415. https://doi.org/10.1186/s12885-016-2467-y
[31] Lung Cancer; New lung cancer study findings reported from University Hospital. (2013). Biotech Week.
[32] Zhou, X., Sang, M., Liu, W., et al. (2012). LMO4 inhibits p53-mediated proliferative inhibition of breast cancer cells through interacting p53. Life Sciences, 91(9–10), 358–363. https://doi.org/10.1016/j.lfs.2012.08.005
[33] Karachaliou, N., Costa, C., Gimenez-Capitan, A., et al. (2012). High mRNA expression of LMO4, a BRCA1 downregulator, correlates with better prognosis in Erlotinib-treated non-small-cell lung cancer (NSCLC) patients (P) with EGFR mutations. Annals of Oncology, 23(S9), ix531. https://doi.org/10.1016/S0923-7534(20)34199-5
[34] Montañez, E. M. M., Scherer, D. D., Li, D. M., et al. (2009). LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progression. Oncogene, 28(41), 3608–3618. https://doi.org/10.1038/onc.2009.221
[35] Yamashita, J., Ozawa, K., Nakanishi, K., et al. (2008). LIM only 4 is overexpressed in late stage pancreas cancer. Molecular Cancer, 7(1), 93. https://doi.org/10.1186/1476-4598-7-93
[36] Wang, N., Kong, K. K. L., Zhang, L., et al. (2007). The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells. Oncogene, 26(44), 6431–6441. https://doi.org/10.1038/sj.onc.1210465
[37] Lu, Z., Lam, S. K., Wang, N., et al. (2006). LMO4 can interact with Smad proteins and modulate transforming growth factor-β signaling in epithelial cells. Oncogene, 25(20), 2920–2930. https://doi.org/10.1038/sj.onc.1209318
[38] Zhang, L., Lam, S. K., Wang, N., et al. (2006). LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells. Oncogene, 25(20), 2920–2930. https://doi.org/10.1038/sj.onc.1209318
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2025-05-16
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