The Circular RNA Circ_0030018/miR-136/migration and Invasion Enhancer 1 (MIEN1) Axis Promotes the Progression of Polycystic Ovary Syndrome

Overview

Journal Bioengineered

Date 2022 Feb 21

PMID 35184658

Authors

Jing Xu

Qinghua Qu

Bao Liu

Liyuan Shen

Affiliations

Soon will be listed here.

Abstract

The abnormal expression of circular RNAs (circRNAs) is associated with the progression of polycystic ovary syndrome (PCOS), which commonly causes infertility in women. In this study, we identified the role of circ_0030018 in PCOS. Quantitative polymerase chain reaction (qPCR) was used to detect the expression levels of circ_0030018, microRNA (miR)-136, and migration and invasion enhancer 1 (MIEN1). Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to analyze the proliferation of KGN cells. Apoptosis was analyzed using fluorescence-activated cell sorting. Transwell assays were performed to measure the migration and invasion abilities of cells. qPCR and Western blotting were used to measure the levels of E-cadherin, N-cadherin, Snail, and vimentin. The correlation of circ_0030018 or MIEN1 expression with miR-136 expression was confirmed via luciferase reporter and RNA pull-down assays. Results showed that circ_0030018 expression was upregulated in patients with PCOS and KGN cells. Knockdown of circ_0030018 suppressed the proliferation, migration, and invasion of cells, while promoting their apoptosis. circ_0030018 sponged miR-136, which targeted MIEN1. Moreover, downregulation of miR-136 abrogated the effects of circ_0030018 silencing, while the overexpression of MIEN1 reversed the miR-136-induced effect on KGN cells. In summary, loss of circ_0030018 delayed the progression of PCOS via the miR-136/MIEN1 axis.

Citing Articles

Circular RNAs as a novel class of potential therapeutic and diagnostic biomarkers in reproductive biology/diseases.

Song W, Chen X, Wu H, Rahimian N Eur J Med Res. 2024; 29(1):643.

PMID: 39741306 PMC: 11689626. DOI: 10.1186/s40001-024-02230-7.

Biomarker potential of competing endogenous RNA networks in Polycystic Ovary Syndrome (PCOS).

Heidarzadehpilehrood R, Pirhoushiaran M Noncoding RNA Res. 2024; 9(2):624-640.

PMID: 38571815 PMC: 10988127. DOI: 10.1016/j.ncrna.2024.01.002.

Role of circular RNA/miRNA axes in the pathophysiology of polycystic ovary syndrome.

Ahmadi M, Fathi M, Malmir A, Ghafouri-Fard S Mol Biol Rep. 2024; 51(1):437.

PMID: 38520572 DOI: 10.1007/s11033-024-09376-x.

The Role of MicroRNA, Long Non-Coding RNA and Circular RNA in the Pathogenesis of Polycystic Ovary Syndrome: A Literature Review.

Nasser J, Altahoo N, Almosawi S, Alhermi A, Butler A Int J Mol Sci. 2024; 25(2).

PMID: 38255975 PMC: 10815174. DOI: 10.3390/ijms25020903.

Circular RNA as a Novel Regulator and Promising Biomarker in Polycystic Ovary Syndrome.

Jing T, Wu Y, Wan A, Ge C, Chen Z, Du Y Biomolecules. 2023; 13(7).

PMID: 37509138 PMC: 10377156. DOI: 10.3390/biom13071101.

References

Dumesic D, Lobo R . Cancer risk and PCOS. Steroids. 2013; 78(8):782-5. DOI: 10.1016/j.steroids.2013.04.004. View

Escobar-Morreale H . Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018; 14(5):270-284. DOI: 10.1038/nrendo.2018.24. View

Ma Z, Zhao H, Zhang Y, Liu X, Hao C . Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome. Arch Gynecol Obstet. 2019; 299(6):1715-1725. DOI: 10.1007/s00404-019-05122-y. View

Lou J, Hao Y, Lin K, Lyu Y, Chen M, Wang H . Circular RNA CDR1as disrupts the p53/MDM2 complex to inhibit Gliomagenesis. Mol Cancer. 2020; 19(1):138. PMC: 7487905. DOI: 10.1186/s12943-020-01253-y. View

Jaseem Khan M, Ullah A, Basit S . Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives. Appl Clin Genet. 2020; 12:249-260. PMC: 6935309. DOI: 10.2147/TACG.S200341. View

Wang L, Long H, Zheng Q, Bo X, Xiao X, Li B . Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol Cancer. 2019; 18(1):119. PMC: 6639939. DOI: 10.1186/s12943-019-1046-7. View

Goodarzi M, Dumesic D, Chazenbalk G, Azziz R . Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011; 7(4):219-31. DOI: 10.1038/nrendo.2010.217. View

Chu Y, Hu X, Wang G, Wang Z, Wang Y . Downregulation of miR-136 promotes the progression of osteosarcoma and is associated with the prognosis of patients with osteosarcoma. Oncol Lett. 2019; 17(6):5210-5218. PMC: 6507308. DOI: 10.3892/ol.2019.10203. View

Kushwaha P, Gupta S, Singh A, Kumar S . Emerging Role of Migration and Invasion Enhancer 1 (MIEN1) in Cancer Progression and Metastasis. Front Oncol. 2019; 9:868. PMC: 6738349. DOI: 10.3389/fonc.2019.00868. View

10.

Li M, Zeng Z, Zhang A, Ye Q, Su S, Xia T . WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs. Int J Gen Med. 2021; 14:8737-8751. PMC: 8627285. DOI: 10.2147/IJGM.S335108. View

11.

Zhao C, Zhou Y, Shen X, Gong M, Lu Y, Fang C . Circular RNA expression profiling in the fetal side of placenta from maternal polycystic ovary syndrome and circ_0023942 inhibits the proliferation of human ovarian granulosa cell. Arch Gynecol Obstet. 2020; 301(4):963-971. DOI: 10.1007/s00404-020-05495-5. View

12.

Kristensen L, Andersen M, Stagsted L, Ebbesen K, Hansen T, Kjems J . The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019; 20(11):675-691. DOI: 10.1038/s41576-019-0158-7. View

13.

Liu J, Ding J, Qu B, Liu J, Song X, Suo Q . CircPSMC3 alleviates the symptoms of PCOS by sponging miR-296-3p and regulating PTEN expression. J Cell Mol Med. 2020; 24(18):11001-11011. PMC: 7521274. DOI: 10.1111/jcmm.15747. View

14.

Zhang C, Wang L, Chen J, Song F, Guo Y . Differential Expression of miR-136 in Gestational Diabetes Mellitus Mediates the High-Glucose-Induced Trophoblast Cell Injury through Targeting E2F1. Int J Genomics. 2020; 2020:3645371. PMC: 7603599. DOI: 10.1155/2020/3645371. View

15.

Zhang C, Liu J, Lai M, Li J, Zhan J, Wen Q . Circular RNA expression profiling of granulosa cells in women of reproductive age with polycystic ovary syndrome. Arch Gynecol Obstet. 2019; 300(2):431-440. PMC: 6592967. DOI: 10.1007/s00404-019-05129-5. View

16.

Lu X, Gao H, Zhu B, Lin G . Circular RNA circ_RANBP9 exacerbates polycystic ovary syndrome via microRNA-136-5p/ axis. Bioengineered. 2021; 12(1):6748-6758. PMC: 8806864. DOI: 10.1080/21655979.2021.1964157. View

17.

Hsu C, Shen T, Chang C, Chang Y, Huang L . Solution structure of the oncogenic MIEN1 protein reveals a thioredoxin-like fold with a redox-active motif. PLoS One. 2013; 7(12):e52292. PMC: 3527542. DOI: 10.1371/journal.pone.0052292. View

18.

Wang C, Tang D, Wang H, Hu G, Hu S, Li L . Circular RNA hsa_circ_0030018 acts as a sponge of miR-599 to aggravate esophageal carcinoma progression by regulating ENAH expression. J Cell Biochem. 2019; 121(8-9):3730-3738. DOI: 10.1002/jcb.29507. View

19.

Mu L, Sun X, Tu M, Zhang D . Non-coding RNAs in polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2021; 19(1):10. PMC: 7807442. DOI: 10.1186/s12958-020-00687-9. View

20.

Jia C, Wang S, Yin C, Liu L, Zhou L, Ma Y . Loss of hsa_circ_0118530 inhibits human granulosa-like tumor cell line KGN cell injury by sponging miR-136. Gene. 2020; 744:144591. DOI: 10.1016/j.gene.2020.144591. View