miR-26b regulates cell proliferation and apoptosis of CD117+CD44+ ovarian cancer stem cells by targeting PTEN

  • Zubiao Gao Department of Obstetrics and Gynecology, Foshan Chancheng Central Hospital, Foshan, Guangdong, China.
  • Xiaofeng Ye Department of Obstetrics and Gynecology, Foshan Chancheng Central Hospital, Foshan, Guangdong, China.
  • Anne Bordeaux Department of Pathology, Medical Center, University of Freiburg, Baden-Wuerttemberg, Germany.
  • Stanka Hettich Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Baden-Wuerttemberg, Germany.
  • Siyao Lin Department of Obstetrics and Gynecology, Foshan Chancheng Central Hospital, Foshan, Guangdong, China.
  • Fang Han | hanfang@gmx.com Department of Obstetrics and Gynecology, Foshan Chancheng Central Hospital, Foshan, Guangdong, China. https://orcid.org/0000-0001-7709-3725
  • Yan Jia Department of Reproductive Immunology, Chengdu Xi’ nan Gynecology Hospital, Chengdu, Sichuan, China.

Abstract

Ovarian cancer (OC) is the one of the most common cancer in women globally. However, it still represents the most dangerous gynecologic malignancy even with the advances in detection and therapeutics. Thus, there is an urgent need in finding more effective therapeutic options for OC patients including cancer stem cells (CSC). MicroRNAs (miRNAs) are small, endogenous, and non-coding RNAs that play critical roles in the progression of various types of tumor. Our aim of this study was to find the regulatory function of microRNA-26 (miRNA-26b) on the cell proliferation and apoptosis of ovarian CSCs. Our studies show that miR-26b is under-regulated in human CD117+CD44+ ovarian CSCs. The miR-26b overexpression inhibits the cell proliferation and promotes cell apoptosis. Moreover, phosphatase and tensin homolog (PTEN) is found to be a functional target of miR-26b. Moreover, PTEN overexpression reversed the effects of miR-26b on the cell proliferation and apoptosis. PTEN overexpression remarkably accelerated the cell proliferation, and inhibited cell apoptosis. These results indicate that miR-26b regulates cell proliferation and apoptosis of CD117+CD44+ ovarian CSCs by targeting PTEN.>

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

References

Grzelak MM, Wrobel PM, Lankosz M, Stegowski Z, Chmura L, Adamek D, et al. Diagnosis of ovarian tumour tissues by SR-FTIR spectroscopy: A pilot study. Spectrochim Acta A Mol Biomol Spectrosc 2018;203:48-55. DOI: https://doi.org/10.1016/j.saa.2018.05.070

Vargas-Hernandez VM, Moreno-Eutimio MA, Acosta-Altamirano G, Vargas-Aguilar VM. Management of recurrent epithelial ovarian cancer. Gland Surg 2014;3:198-202.

Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 2008;68:4311-20. DOI: https://doi.org/10.1158/0008-5472.CAN-08-0364

Zhao B, Yu Q, Li H, Guo X, He X. Characterization of microRNA expression profiles in patients with intervertebral disc degeneration. Int J Mol Med 2014;33:43-50. DOI: https://doi.org/10.3892/ijmm.2013.1543

Chen D, Zhang Y, Wang J, Chen J, Yang C, Cai K, et al. MicroRNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ ovarian cancer stem cells by regulating epithelial-mesenchymal transition. J Ovarian Res 2013;6:50. DOI: https://doi.org/10.1186/1757-2215-6-50

Zhuang RJ, Bai XX, Liu W. MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2. Cancer Biol Ther 2019;20:897-911. DOI: https://doi.org/10.1080/15384047.2019.1579960

Dang X, Ma A, Yang L, Hu H, Zhu B, Shang D, et al. MicroRNA-26a regulates tumorigenic properties of EZH2 in human lung carcinoma cells. Cancer Genet 2012;205:113-23. DOI: https://doi.org/10.1016/j.cancergen.2012.01.002

Lu J, He ML, Wang L, Chen Y, Liu X, Dong Q, et al. MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2. Cancer Res 2011;71:225-33. DOI: https://doi.org/10.1158/0008-5472.CAN-10-1850

Sun J, Tian X, Lu SQ, Hu HB. MicroRNA-4465 suppresses tumor proliferation and metastasis in non-small cell lung cancer by directly targeting the oncogene EZH2. Biomed Pharmacother 2017;96:1358-62. DOI: https://doi.org/10.1016/j.biopha.2017.11.070

He Y, Liu H, Jiang L, Rui B, Mei J, Xiao H. miR-26 Induces apoptosis and inhibits autophagy in non-small cell lung cancer cells by suppressing TGF-beta1-JNK signaling pathway. Front Pharmacol 2018;9:1509. DOI: https://doi.org/10.3389/fphar.2018.01509

Papa A, Pandolfi PP. The PTEN(-)PI3K axis in cancer. Biomolecules 2019;9:153. DOI: https://doi.org/10.3390/biom9040153

Yang Y, Bai Y, He Y, Zhao Y, Chen J, Ma L, et al. PTEN loss promotes intratumoral androgen synthesis and tumor microenvironment remodeling via aberrant activation of RUNX2 in castration-resistant prostate cancer. Clin Cancer Res 2018;24:834-46. DOI: https://doi.org/10.1158/1078-0432.CCR-17-2006

Zhao D, Chen Y, Chen S, Zheng C, Hu J, Luo S. MiR-19a regulates the cell growth and apoptosis of osteosarcoma stem cells by targeting PTEN. Tumour Biol 2017;39:1010428317705341. DOI: https://doi.org/10.1177/1010428317705341

Dong YX, Pang ZG, Zhang JC, Hu JQ, Wang LY. Long non-coding RNA GClnc1 promotes progression of colorectal cancer by inhibiting p53 signaling pathway. Eur Rev Med Pharmacol Sci 2019;23:5705-13.

Chen J, Wang J, Chen D, Yang J, Yang C, Zhang Y, et al. Evaluation of characteristics of CD44+CD117+ ovarian cancer stem cells in three dimensional basement membrane extract scaffold versus two dimensional monocultures. BMC Cell Biol 2013;14:7. DOI: https://doi.org/10.1186/1471-2121-14-7

Dou J, Pan M, Wen P, Li Y, Tang Q, Chu L, et al. Isolation and identification of cancer stem-like cells from murine melanoma cell lines. Cell Mol Immunol 2007;4:467-72.

Arnhold S, Gluer S, Hartmann K, Raabe O, Addicks K, Wenisch S, et al. Amniotic-fluid stem cells: Growth dynamics and differentiation potential after a CD-117-based selection procedure. Stem Cells Int 2011;2011:715341. DOI: https://doi.org/10.4061/2011/715341

Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, et al. Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol 2011;91:596-602. DOI: https://doi.org/10.1016/j.yexmp.2011.06.005

Yin Q, Fischer L, Noethling C, Schaefer WR. In vitro-assessment of putative antiprogestin activities of phytochemicals and synthetic UV absorbers in human endometrial Ishikawa cells. Gynecol Endocrinol 2015;31:578-81. DOI: https://doi.org/10.3109/09513590.2015.1047448

Zhang L, Huang C, Guo Y, Gou X, Hinsdale M, Lloyd P, et al. MicroRNA-26b modulates the NF-kappaB pathway in alveolar macrophages by regulating PTEN. J Immunol 2015;195:5404-14. DOI: https://doi.org/10.4049/jimmunol.1402933

Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014;14:275-91. DOI: https://doi.org/10.1016/j.stem.2014.02.006

Vezzoni L, Parmiani G. Limitations of the cancer stem cell theory. Cytotechnology 2008;58:3-9. DOI: https://doi.org/10.1007/s10616-008-9166-8

Xia Q, Han T, Yang P, Wang R, Li H, Zhang J, et al. MicroRNA-28-5p regulates liver cancer stem cell expansion via IGF-1 pathway. Stem Cells Int 2019;2019:8734362. DOI: https://doi.org/10.1155/2019/8734362

Khosla R, Hemati H, Rastogi A, Ramakrishna G, Sarin SK, Trehanpati N. miR-26b-5p helps in EpCAM+cancer stem cells maintenance via HSC71/HSPA8 and augments malignant features in HCC. Liver Int 2019;39:1692-703. DOI: https://doi.org/10.1111/liv.14188

Wu K, Mu XY, Jiang JT, Tan MY, Wang RJ, Zhou WJ, et al. miRNA26a5p and miR26b5p inhibit the proliferation of bladder cancer cells by regulating PDCD10. Oncol Rep 2018;40:3523-32.

Fan D, Lin X, Zhang F, Zhong W, Hu J, Chen Y, et al. MicroRNA 26b promotes colorectal cancer metastasis by downregulating phosphatase and tensin homolog and wingless-type MMTV integration site family member 5A. Cancer Sci 2018;109:354-62. DOI: https://doi.org/10.1111/cas.13451

Kim RJ, Bae E, Hong YK, Hong JY, Kim NK, Ahn HJ, et al. PTEN loss-mediated Akt activation increases the properties of cancer stem-like cell populations in prostate cancer. Oncology 2014;87:270-9. DOI: https://doi.org/10.1159/000363186

Hai Ping P, Feng Bo T, Li L, Nan Hui Y, Hong Z. IL-1beta/NF-kb signaling promotes colorectal cancer cell growth through miR-181a/PTEN axis. Arch Biochem Biophys 2016;604:20-6. DOI: https://doi.org/10.1016/j.abb.2016.06.001

Published
2021-02-04
Info
Issue
Section
Articles
Keywords:
miR-26b, PTEN, ovarian cancer stem cells (CSCs), cell proliferation, apoptosis
Statistics
  • Abstract views: 145

  • PDF: 103
  • HTML: 0
How to Cite
Gao, Z., Ye, X., Bordeaux, A., Hettich, S., Lin, S., Han, F., & Jia, Y. (2021). miR-26b regulates cell proliferation and apoptosis of CD117+CD44+ ovarian cancer stem cells by targeting PTEN. European Journal of Histochemistry, 65(1). https://doi.org/10.4081/ejh.2021.3186