Clinical and biological significance of microRNA-127 and microRNA-138 expression in women with breast cancer: response to treatment and survival impact
Tóm tắt
Genetic and epigenetic changes characterize the multi-step process of breast carcinogenesis. It is believed that abnormal microRNA (miRNA) expression has a role in the onset and progression of breast cancer. This study aimed to examine the link between miRNA-127 and miRNA-138 and metastasis, tumor invasion, and apoptosis in Egyptian women with breast cancer, as well as their correlation with its molecular types. A total of 150 participants were included in this study, including 75 women with breast cancer and 75 supposedly healthy women who were age and gender-matched. Every patient underwent a thorough physical examination, a general clinical examination, a mammogram, and lab tests, such as the determination of the levels of miRNA-127 and miRNA-138 expression by real-time PCR and the measurement of blood carcinoembryonic antigen (CEA) and carcinoma antigen 15–3 (CA15-3) and CA15-3 and CEA levels. There was a significant low expression of miRNA-127 in favor of high TNM stage (Classification of Malignant Tumors), left-sided tumor, metastasis, high-grade disease, increased axillary nodal involvement, absence of estrogen and progesterone receptors, and low antigen Kiel 67 (Ki67) expression. Also, a significant expression of miRNA 127 in triple-negative breast cancer was found, followed by human epidermal growth factor receptor 2 (HER2/neu) overexpression, then luminal B, and the highest expression was with the Luminal A molecular subtype. A significant negative correlation existed between miRNA 127 and miRNA 138 with CEA and CA15.3 levels. The miRNA-127 and miRNA-138 suppression may promote metastasis. Consequently, the restoration of miRNA-127 and miRNA-138 in breast cancer may have therapeutic potential; so, the miRNA-127 and miRNA-138 may play a role in breast cancer development.
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Tài liệu tham khảo
Abdel-Fadeel N, Zanaty M, Kamal A, Hassan M, Taha M (2022) Childhood psychological trauma and psychiatric comorbidity in patients with breast cancer. Egypt J Hosp Med 88(1):2788–2794. https://doi.org/10.21608/ejhm.2022.241954
Almohaywi M, Sugita BM, Centa A, Fonseca AS, Antunes VC, Fadda P, Mannion CM, Abijo T, Goldberg SL, Campbell MC, Copeland RL, Kanaan Y, Cavalli LR (2023) Deregulated miRNA expression in triple-negative breast cancer of ancestral genomic-characterized latina patients. Int J Mol Sci 24(17):13046. https://doi.org/10.3390/ijms241713046
Alizadeh S, Isanejad A, Sadighi S, Khalighfard S, Alizadeh AM (2019) Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy A single-blind randomized trial. Annals Phys Rehabilit Med 62(5):329–335. https://doi.org/10.1016/j.rehab.2019.07.001
Chen J, Wang M, Guo M, Xie Y, Cong YS (2013) miR-127 regulates cell proliferation and senescence by targeting BCL6. PLoS ONE 8(11):e80266
Cheng H, Chen L, Fang Z, Wan Q, Du Z, Ma N, Guo G, Lu W (2022) The effect of miRNA-138 on the proliferation and apoptosis of breast cancer cells through the NF-κB/VEGF signaling pathway. Cellular Mole Biol Noisy-le-Grand, France 68(2):132–137. https://doi.org/10.14715/cmb/2022.68.2.19
El Hejjioui B, Lamrabet S, Amrani Joutei S, Senhaji N, Bouhafa T, Malhouf MA, Bennis S, Bouguenouch L (2023) New biomarkers and treatment advances in triple-negative breast cancer. Diagnostics (Basel, Switzerland) 13(11):1949. https://doi.org/10.3390/diagnostics13111949
Guo LH, Li H, Wang F, Yu J, He JS (2013) The tumor suppressor roles of miR-433 and miR-127 in gastric cancer. Int J Mol Sci 14(7):14171–14184
Han J, Mendell JT (2023) MicroRNA turnover: a tale of tailing, trimming, and targets. Trends Biochem Sci 48(1):26–39. https://doi.org/10.1016/j.tibs.2022.06.005
Khadka VS, Nasu M, Deng Y, Jijiwa M (2023) Circulating microRNA biomarkers for detecting breast cancer in high-risk benign breast tumors. Int J Mol Sci 24(8):7553. https://doi.org/10.3390/ijms24087553
Li D, Song H, Wu T et al (2017) MiRNA-138-5p targeting LIMK1 suppresses breast cancer cell proliferation and motility. Rsc Adv 7(82):52030–52038
Lu M, Ju S, Shen X, Wang X, Jing R, Yang C, Chu H, Cong H (2017) Combined detection of plasma miRNA-127-3p and HE4 improves the diagnostic efficacy of breast cancer. Cancer Biomark 18(2):143–148. https://doi.org/10.3233/CBM-160024
Nama S, Muhuri M, Di Pascale F, Quah S, Aswad L, Fullwood M, Sampath P (2019) MicroRNA-138 is a prognostic biomarker for triple-negative breast cancer and promotes tumorigenesis via TUSC2 repression. Sci Rep 9(1):12718. https://doi.org/10.1038/s41598-019-49155-4
Pronina IV, Loginov VI, Burdennyy AM, Fridman MV, Senchenko VN, Kazubskaya TP, Kushlinskii NE, Dmitriev AA, Braga EA (2017) DNA methylation contributes to the deregulation of 12 cancer-associated microRNAs and breast cancer progression. Gene 604:1–8. https://doi.org/10.1016/j.gene.2016.12.018
Qattan A (2020) Novel miRNA targets and therapies in the triple-negative breast cancer microenvironment: an emerging hope for a challenging disease. Int J Mol Sci 21(23):8905. https://doi.org/10.3390/ijms21238905
Sha HH, Wang DD, Chen D, Liu SW, Wang Z, Yan DL, Feng JF (2017) MiR-138: A promising therapeutic target for cancer. Tumor Biol 39(4):1010428317697575
Shang C, Chen Q, Zu F, Ren W (2022) Integrated analysis identified prognostic microRNAs in breast cancer. BMC Cancer 22(1):1170. https://doi.org/10.1186/s12885-022-10242-x
Shinde SS, Ahmed S, Malik JA, Hani U, Khanam A, Ashraf Bhat F, Ahmad MiRNA S, Ghazwani M, Wahab S, Haider N, Almehizia AA (2023) Therapeutic delivery of tumor suppressor miRNAs for breast cancer treatment. Biology 12(3):467. https://doi.org/10.3390/biology12030467
Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics. CA: A Cancer J Clin 71(1):7–33. https://doi.org/10.3322/caac.21654
Teh BT, Fearon ER (2020) Genetic and epigenetic alterations in cancer. Abeloff’s Clin Oncol 209–224:e2. https://doi.org/10.1016/b978-0-323-47674-4.00014-1
Thu HN, Vy HT, Thanh TN, Giang DT, Nhan TN, Hoang NP, Hue TN (2021) miRNA-16 as an internal control in breast cancer studies: a systematic review and meta-analysis. Mol Biol 55(6):1045–1056. https://doi.org/10.31857/S0026898421060136
Umeh-Garcia M, Simion C, Ho PY, Batra N, Berg AL, Carraway KL, Yu A, Sweeney C (2020) A Novel Bioengineered miRNA-127 Prodrug Suppresses the Growth and Metastatic Potential of Triple-Negative Breast Cancer Cells. Can Res 80(3):418–429. https://doi.org/10.1158/0008-5472.CAN-19-0656
Wang G, Dong Y, Liu H, Ji N, Cao J, Liu A, Tang X, Ren Y (2022) Long noncoding RNA (lncRNA) metallothionein 1 J, pseudogene (MT1JP) is downregulated in triple-negative breast cancer and upregulates microRNA-138 (miRNA-138) to downregulate hypoxia-inducible factor-1α (HIF-1α). Bioengineered 13(5):13718–13727. https://doi.org/10.1080/21655979.2022.2077906
Wang S, Li H, Wang J, Wang D, Yao A, Li Q (2014) Prognostic and biological significance of microRNA-127 expression in human breast cancer. Dis Markers 2014:401986. https://doi.org/10.1155/2014/401986
Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Shao JY (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis, and patient poor prognosis. RNA 14(11):2348–2360
Yao L, Chen L, Zhou H, Duan F, Wang L, Zhang Y (2022) Long noncoding RNA NEAT1 promotes the progression of breast cancer by regulating miRNA-138-5p/ZFX axis. Cancer Biother Radiopharm 37(8):636–649. https://doi.org/10.1089/cbr.2019.3515
Yedigaryan L, Sampaolesi M (2021) Therapeutic implications of miRNAs for muscle-wasting conditions. Cells 10(11):3035. https://doi.org/10.3390/cells10113035
Yeh M, Oh CS, Yoo JY, Kaur B, Lee TJ (2019) Pivotal role of microRNA-138 in human cancers. Am J Cancer Res 9(6):1118–1126
Zhang J, Liu D, Feng Z, Mao J, Zhang C, Lu Y, Li J, Zhang Q, Li Q, Li L (2016) MicroRNA-138 modulates metastasis and EMT in breast cancer cells by targeting vimentin. Biomed Pharmacother Biomed Pharmacother 77:135–141. https://doi.org/10.1016/j.biopha.2015.12.018
Zhao C, Ling X, Li X, Hou X, Da Z (2019) MicroRNA-138-5p inhibits cell migration, invasion, and EMT in breast cancer by directly targeting RHBDD1. Breast Cancer 26(6):817–825. https://doi.org/10.1007/s12282-019-00989-w
Zhao X, Duan Z, Liu X, Wang B, Wang X, He J, Yao Z, Yang J (2013) MicroRNA-127 is downregulated by Tudor-SN protein and contributes to metastasis and proliferation in breast cancer cell line MDA-MB-231. Anat Rec (Hoboken) 296(12):1842–1849