Abstract
MicroRNAs act as regulators in ovarian tumorigenesis and progression by involving different molecular pathways. Here, we examined the role of miR-135b on growth, chemotherapy resistance in OVCAR3 and SKOV3 ovarian cancer cells. MTT assay was performed to examine proliferation. Transwell migration and matrigel invasion assays were used to assess migration and invasion. Caspase-Glo3/7 assay was carried out to evaluate apoptosis. The dual-luciferase reporter assay was performed to validate the putative binding site. Meanwhile, the miR-135b levels in human ovarian cancer tissue were detected by qPCR assay. Overexpression of miR-135b increased growth, and improved migration and invasion in ovarian cancer cells. Meanwhile, overexpression of miR-135b decreased the cisplatin treatment sensitivity in OVCAR3 and SKOV3 cells. The cisplatin-induced apoptosis was decreased by miR-135b. Furthermore, miR-135b could alter epithelial to mesenchymal transition (EMT) associated proteins expression including E-cadherin, N-cadherin, snail and Vimentin in ovarian cancer cells. Further study demonstrated aberrant expression of miR-135b regulated PTEN and p-AKT expression in ovarian cancer cells. The expression level of miR-135b was increased in human ovarian cancer tissue, compared with normal ovary tissue. MiR-135b involves in tumorigenesis and progression in ovarian cancer cells, and might serve as a promising biomarker to predict chemotherapy sensitivity and prognosis in ovarian cancer.
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The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
References
Cai J, Xu L, Tang H et al (2014) The role of the PTEN/PI3K/Akt pathway on prognosis in epithelial ovarian cancer: a meta-analysis. Oncologist 19(5):528–535
Cristea M, Han E, Salmon L, Morgan RJ (2010) Practical considerations in ovarian cancer chemotherapy. Therapeutic Adv Med Oncol 2(3):175–187
Dasari S, Tchounwou PB (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378
Di Leva G, Croce CM (2013) The Role of microRNAs in the Tumorigenesis of Ovarian Cancer. Front Oncol 3:153
Li SD, Zhang JR, Wang YQ, Wan XP (2010) The role of microRNAs in ovarian cancer initiation and progression. J Cell Mol Med 14(9):2240–2249
Luo X, Dong Z, Chen Y, Yang L, Lai D (2013) Enrichment of ovarian cancer stem-like cells is associated with epithelial to mesenchymal transition through an miRNA-activated AKT pathway. Cell Prolif 46(4):436–446
Macfarlane LA, Murphy PR (2010) MicroRNA: Biogenesis, Function and Role in Cancer. Curr Genom 11(7):537–561
Mihailescu R (2015) Gene expression regulation: lessons from noncoding RNAs. RNA 21(4):695–696
Nana-Sinkam SP, Croce CM (2014) MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: towards clinical use. Genome Biol 15(9):445
Rauh-Hain JA, Krivak TC, Del Carmen MG, Olawaiye AB (2011) Ovarian cancer screening and early detection in the general population. Rev Obstet Gynecol 4(1):15–21
Russo A, Czarnecki AA, Dean M et al (2018) PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation. Oncogene 37(15):1976–1990
Shen DW, Pouliot LM, Hall MD, Gottesman MM (2012) Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev 64(3):706–721
Soyama H, Takano M, Miyamoto M et al (2017) Factors favouring long-term survival following recurrence in ovarian cancer. Mol Clin Oncol 7(1):42–46
Torre LA, Islami F, Siegel RL, Ward EM, Jemal A (2017) Global Cancer in Women: Burden and Trends. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research. cosponsored by the American Society of Preventive Oncology 26(4):444–457
Wang Y, Zhao S, Zhu L, Zhang Q, Ren Y (2018) MiR-19a negatively regulated the expression of PTEN and promoted the growth of ovarian cancer cells. Gene 670:166–173
Smith CG (2017) A Resident’s Perspective of Ovarian Cancer. Diagnostics 7(2)
Torre LA, Trabert B, DeSantis CE, et al (2018) Ovarian cancer statistics. CA a cancer journal for clinicians 68(4): 284 – 96
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JW and RZ: performed experiments, write manuscript. BZ, JL and LZ: performed experiments, prepare figures and table. WJ and XL: Collected patient tissue, performed experiments. XD: design the project, write manuscript and statistical analysis. All authors reviewed the manuscript.
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Ethical committee of Jilin University approved this study. The informed consents were signed by all patients. All methods were performed in accordance with the relevant guidelines and regulations by the Ethical committee of Jilin University.
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10735_2022_10080_MOESM1_ESM.tiff
Supplementary file1 The graph indicated Ki67 positive cells (A) and PTEN positive cells (B) in normalovarian tissue, ovarian cancer tissue with low-level miR-135b and ovarian cancer tissue with high-level miR-135b (TIFF 24.7 kb)
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Wang, J., Zhang, R., Zhang, B. et al. MiR-135b improves proliferation and regulates chemotherapy resistance in ovarian cancer. J Mol Histol 53, 699–712 (2022). https://doi.org/10.1007/s10735-022-10080-y
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DOI: https://doi.org/10.1007/s10735-022-10080-y