Keywords
microRNA
miR-125b
demographic
Malaysia
How to Cite
Abstract
Breast cancer (BC), the most prevalent and fatal female neoplasm worldwide, including in Malaysia, is a heterogeneous disease classified into subtypes based on hormone receptor status, including luminal A, luminal B, HER2-enriched and triple-negative. The heterogeneity of BC poses challenges for accurate diagnosis and treatment, necessitating novel biomarkers to aid cancer screening, diagnosis and therapy. MicroRNAs (miRNAs), which regulate gene expression, are often dysregulated in cancer. Specifically, miR-125b has been linked to mitochondrial dysfunction and chemoresistance, supporting its potential as a biomarker for BC, particularly as a predictive biomarker. This study aims to investigate the associations between miR-125b expression patterns in different BC subtypes and demographic profiles at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia (HCTM). miR-125b expression was analysed in 18 formalin-fixed paraffin-embedded (FFPE) BC tissue samples and two control tissues by quantitative polymerase chain reaction (qPCR). Among 241 BC cases reported at HCTM in 2023, patients were predominantly Malay, aged 50 and above, with luminal A being the most common subtype, followed by triple-negative, luminal B and HER2-enriched. miR-125b expression was consistently downregulated in BC tissues compared to controls, although this difference was not statistically significant (p = 0.263). Trends of downregulation were observed across all subtypes and demographic groups, with no significant differences by age (p = 1.000), ethnicity (p = 0.546) or BC subtypes (p = 0.701). The consistent downregulation of miR-125b aligns with previous studies and highlights its biomarker potential for BC diagnosis and prognosis. Further research with a larger cohort is needed to validate these findings and explore the potential of miR-125b as a diagnostic, prognostic or predictive biomarker in BC.
References
Arun, R. P., Cahill, H. F., & Marcato, P. (2022). Breast cancer subtype-specific miRNAs: Networks, impacts, and the potential for intervention. Biomedicines, 10(3), 651.
https://doi.org/10.3390/biomedicines10030651
Bhoo-Pathy, N., Hartman, M., Yip, C. H., Saxena, N., Taib, N. A., Lim, S. E., Iau, P., Adami, H. O., Bulgiba, A. M., Lee, S. C., & Verkooijen, H. M. (2012). Ethnic differences in survival after breast cancer in South East Asia. PLoS ONE, 7(2), e30995.
https://doi.org/10.1371/journal.pone.0030995
Devi, C. R. B., Tang, T. S., & Corbex, M. (2012). Incidence and risk factors for breast cancer subtypes in three distinct South-East Asian ethnic groups: Chinese, Malay and natives of Sarawak, Malaysia. International Journal of Cancer, 131(12), 2869–2877.
https://doi.org/10.1002/ijc.27527
Feliciano, A., Castellvi, J., Artero-Castro, A., Leal, J. A., Romagosa, C., Hernández-Losa, J., Peg, V., Fabra, A., Vidal, F., Kondoh, H., Ramón y Cajal, S., & Lleonart, M. E. (2013). miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-α, CCNJ, and MEGF9. PLoS ONE, 8(10).
https://doi.org/10.1371/journal.pone.0076247
Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Piñeros, M., Znaor, A., Soerjomataram, I., & Bray, F. (2024). Global cancer observatory: Cancer today. International Agency for Research on Cancer.
https://gco.iarc.who.int/today
Hu, G., Zhao, X., Wang, J., Lv, L., Wang, C., Feng, L., Shen, L., & Ren, W. (2018). miR-125b regulates the drug-resistance of breast cancer cells to doxorubicin by targeting HAX-1. Oncology Letters, 15(2), 1621–1629.
https://doi.org/10.3892/ol.2017.7476
Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., Magri, E., Pedriali, M., Fabbri, M., Campiglio, M., Ménard, S., Palazzo, J. P., Rosenberg, A., Musiani, P., Volinia, S., Nenci, I., Calin, G. A., Querzoli, P., Negrini, M., & Croce, C. M. (2005). MicroRNA gene expression eregulation in human breast cancer. Cancer Research, 65(16), 7065–7070.
https://doi.org/10.1158/0008-5472.can-05-1783
Kolesnikov, N. N., Veryaskina, Y. A., Titov, S. E., Rodionov, V. V., Gening, T. P., Abakumova, T. V., Kometova, V. V., Torosyan, M. K., & Zhimulev, I. F. (2019). Expression of micrornas in molecular genetic breast cancer subtypes. Cancer Treatment and Research Communications, 20, 100026.
https://doi.org/10.1016/j.ctarc.2016.08.006
Llanos, A. A. M., Chandwani, S., Bandera, E. V., Hirshfield, K. M., Lin, Y., Ambrosone, C. B., & Demissie, K. (2015). Associations between sociodemographic and clinicopathological factors, and breast cancer subtypes in a population-based study. Cancer Causes & Control, 26(12), 1737.
https://doi.org/10.1007/s10552-015-0667-4
Mar-Aguilar, F., Luna-Aguirre, C. M., Moreno-Rocha, J. C., Araiza-Chávez, J., Trevino, V., Rodríguez-Padilla, C., & Reséndez-Pérez, D. (2013). Differential expression of miR-21, miR-125b and miR-191 in breast cancer tissue. Asia-Pacific Journal of Clinical Oncology, 9(1), 53–59.
https://doi.org/10.1111/j.1743-7563.2012.01548.x
Nie, J., Jiang, H. C., Zhou, Y. C., Jiang, B., He, W. J., Wang, Y. F., & Dong, J. (2019). MiR-125b regulates the proliferation and metastasis of triple negative breast cancer cells via the Wnt/β-catenin pathway and EMT. Bioscience, Biotechnology, and Biochemistry, 83(6), 1062–1071.
https://doi.org/10.1080/09168451.2019.1584521
Orrantia-Borunda, E., Anchondo-Nuñez, P., Lucero, •, Acuña-Aguilar, E., Francisco, •, Gómez-Valles, O., Claudia, •, Ramírez-Valdespino, A., & Adriana Ramírez-Valdespino, C. (2022). Subtypes of breast cancer. Exon Publications, 31–42.
https://doi.org/10.36255/exon-publications-breast-cancer-subtypes
Porporato, P. E., Filigheddu, N., Pedro, J. M. B. S., Kroemer, G., & Galluzzi, L. (2017). Mitochondrial metabolism and cancer. Cell Research, 28(3), 265–280.
https://doi.org/10.1038/cr.2017.155
Tsang, J. Y. S., & Tse, G. M. (2020). Molecular classification of breast cancer. Advances in Anatomic Pathology, 27(1), 27–35.
https://doi.org/10.1097/pap.0000000000000232
Wong, S. R., Pei Pei, C., Islahuddin, M. T. M., Baghawi, A., Ti, G. L., Singaram, N., & Har, L. S. (2024). miR-21 expression and its correlation with demographics, subtypes, and tumour suppressor genes; PTEN and PDCD4 in breast cancer tissues in Malaysia. Eurasian Journal of Medicine and Oncology, 8(1), 59–73.
https://dx.doi.org/10.14744/ejmo.2024.24156
Xie, X., Hu, Y., Xu, L., Fu, Y., Tu, J., Zhao, H., Zhang, S., Hong, R., & Gu, X. (2015). The role of miR-125b-mitochondria-caspase-3 pathway in doxorubicin resistance and therapy in human breast cancer. Tumor Biology, 36(9), 7185–7194.
https://doi.org/10.1007/s13277-015-3438-7
Yang, Z., & Liu, Z. (2020). The emerging role of MicroRNAs in breast cancer. Journal of Oncology, 2020(1), 9160905.
https://doi.org/10.1155/2020/9160905
Zhang, Y., Yan, L. X., Wu, Q. N., Du, Z. M., Chen, J., Liao, D. Z., Huang, M. Y., Hou, J. H., Wu, Q. L., Zeng, M. S., Huang, W. L., Zeng, Y. X., & Shao, J. Y. (2011). miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer. Cancer Research, 71(10), 3552–3562.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Norlizawati Abdul Hamed, Xiao Ning Zhu , Bann Siang Yeo , Wen Xuan Lee , Geok Chin Tan , Yoke Kqueen Cheah