Long non‑coding RNA USP30‑AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA‑299‑3p and thereby overexpressing PTP4A1

Chen,Mengyue; Chi,Yugang; Chen,Hongwei; Zhao,Limei

doi:10.3892/ol.2021.12766

Long non‑coding RNA USP30‑AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA‑299‑3p and thereby overexpressing PTP4A1

Authors:
- Mengyue Chen
- Yugang Chi
- Hongwei Chen
- Limei Zhao
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Affiliations: Department of Gynaecology, The First People's Hospital of Chongqing Liangjiang New Area, Chongqing 401120, P.R. China, Department of Gynaecology and Obstetrics, Chongqing Health Center for Women and Children, Chongqing 400021, P.R. China
Published online on: April 29, 2021 https://doi.org/10.3892/ol.2021.12766
Article Number: 505
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

USP30 antisense RNA 1 (USP30‑AS1) has been studied in bladder urothelial carcinoma. However, the detailed role of USP30‑AS1 in cervical cancer remains to be elucidated. Therefore, the present study determined whether USP30‑AS1 is implicated in cervical cancer malignancy, and investigated relevant molecular mechanisms. USP30‑AS1 expression was measured via reverse transcription‑quantitative PCR. Functional experiments, including the Cell Counting Kit‑8 assay, flow cytometry, Transwell migration and invasion assays, and mouse tumour model, were performed in order to elucidate the roles of USP30‑AS1. The target of USP30‑AS1 was predicted using bioinformatics analysis, which was further verified via RNA immunoprecipitation and luciferase reporter assays. Herein, USP30‑AS1 overexpression was detected in cervical cancer sample data from The Cancer Genome Atlas and our cohort. Patients with cervical cancer expressing high levels of USP30‑AS1 exhibited shorter overall survival than those with low USP30‑AS1 expression. In vitro and in vivo experiments revealed that USP30‑AS1 interference promoted cell apoptosis; restrained cell proliferation, migration and invasion in vitro, and hindered tumour growth in vivo. Mechanistically, USP30‑AS1 competed for microRNA‑299‑3p (miR‑299‑3p) in cervical cancer and lowered the regulatory actions of miR‑299‑3p on protein tyrosine phosphatase type IVA (PTP4A1), resulting in PTP4A1 overexpression. Furthermore, rescue experiments confirmed that miR‑299‑3p interventions or exogenous PTP4A1 could counteract the cancer‑inhibiting actions of USP30‑AS1 silencing on cervical cancer cells. In conclusion, the miR‑299‑3p/PTP4A1 axis is the downstream effector of USP30‑AS1 in cervical cancer, forming the USP30‑AS1/miR‑299‑3p/PTP4A1 pathway. This newly identified competing endogenous RNA pathway may offer a novel theoretical and experimental basis for developing promising new strategies for the targeted therapy of cervical cancer.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Abbas KM, van Zandvoort K, Brisson M and Jit M: Effects of updated demography, disability weights, and cervical cancer burden on estimates of human papillomavirus vaccination impact at the global, regional, and national levels: A PRIME modelling study. Lancet Glob Health. 8:e536–e544. 2020. View Article : Google Scholar : PubMed/NCBI
3	Tsikouras P, Zervoudis S, Manav B, Tomara E, Iatrakis G, Romanidis C, Bothou A and Galazios G: Cervical cancer: Screening, diagnosis and staging. J BUON. 21:320–325. 2016.PubMed/NCBI
4	Nuchpramool P and Hanprasertpong J: Preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are not clinically useful in predicting prognosis in early stage cervical cancer. Surg Res Pract. 2018:91629212018.PubMed/NCBI
5	Venkatas J and Singh M: Cervical cancer: A meta-analysis, therapy and future of nanomedicine. Ecancermedicalscience. 14:11112020.PubMed/NCBI
6	Small W Jr, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN and Gaffney DK: Cervical cancer: A global health crisis. Cancer. 123:2404–2412. 2017. View Article : Google Scholar : PubMed/NCBI
7	Bhan A, Soleimani M and Mandal SS: Long noncoding RNA and cancer: A new paradigm. Cancer Res. 77:3965–3981. 2017. View Article : Google Scholar : PubMed/NCBI
8	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: Insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
9	Kornienko AE, Guenzl PM, Barlow DP and Pauler FM: Gene regulation by the act of long non-coding RNA transcription. BMC Biol. 11:592013. View Article : Google Scholar : PubMed/NCBI
10	DiStefano JK: The emerging role of long noncoding RNAs in human disease. Methods Mol Biol. 1706:91–110. 2018. View Article : Google Scholar : PubMed/NCBI
11	Wapinski O and Chang HY: Long noncoding RNAs and human disease. Trends Cell Biol. 21:354–361. 2011. View Article : Google Scholar : PubMed/NCBI
12	Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A and Rinn JL: Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25:1915–1927. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhang H, Wang Y, Liu X and Li Y: Progress of long noncoding RNAs in anti-tumor resistance. Pathol Res Pract. 216:1532152020. View Article : Google Scholar : PubMed/NCBI
14	Teppan J, Barth DA, Prinz F, Jonas K, Pichler M and Klec C: Involvement of long non-coding RNAs (lncRNAs) in tumor angiogenesis. Noncoding RNA. 6:422020.PubMed/NCBI
15	Ye M, Zhang J, Wei M, Liu B and Dong K: Emerging role of long noncoding RNA-encoded micropeptides in cancer. Cancer Cell Int. 20:5062020. View Article : Google Scholar : PubMed/NCBI
16	Shi D, Zhang C and Liu X: Long noncoding RNAs in cervical cancer. J Cancer Res Ther. 14:745–753. 2018. View Article : Google Scholar : PubMed/NCBI
17	Aalijahan H and Ghorbian S: Long non-coding RNAs and cervical cancer. Exp Mol Pathol. 106:7–16. 2019. View Article : Google Scholar : PubMed/NCBI
18	Sun W, Shen NM and Fu SL: Involvement of lncRNA-mediated signaling pathway in the development of cervical cancer. Eur Rev Med Pharmacol Sci. 23:3672–3687. 2019.PubMed/NCBI
19	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
20	Farazi TA, Hoell JI, Morozov P and Tuschl T: MicroRNAs in human cancer. Adv Exp Med Biol. 774:1–20. 2013. View Article : Google Scholar : PubMed/NCBI
21	Shen S, Zhang S, Liu P, Wang J and Du H: Potential role of microRNAs in the treatment and diagnosis of cervical cancer. Cancer Genet. 248-249:25–30. 2020. View Article : Google Scholar : PubMed/NCBI
22	Miao J, Regenstein JM, Xu D, Zhou D, Li H, Zhang H, Li C, Qiu J and Chen X: The roles of microRNA in human cervical cancer. Arch Biochem Biophys. 690:1084802020. View Article : Google Scholar : PubMed/NCBI
23	Cao D, Wang Y, Li D and Wang L: Reconstruction and analysis of the differentially expressed IncRNA-miRNA-mRNA Network based on competitive endogenous RNA in hepatocellular carcinoma. Crit Rev Eukaryot Gene Expr. 29:539–549. 2019. View Article : Google Scholar : PubMed/NCBI
24	Sun Z, Jing C, Xiao C and Li T: An autophagy-related long non-coding RNA prognostic signature accurately predicts survival outcomes in bladder urothelial carcinoma patients. Aging. 12:15624–15637. 2020. View Article : Google Scholar : PubMed/NCBI
25	Saleh M, Virarkar M, Javadi S, Elsherif SB, de Castro Faria S and Bhosale P: Cervical cancer: 2018 revised international federation of gynecology and obstetrics staging system and the role of imaging. AJR Am J Roentgenol. 214:1182–1195. 2020. View Article : Google Scholar : PubMed/NCBI
26	Cancer Genome Atlas Research Network; Albert Einstein College of Medicine; Analytical Biological Services; Barretos Cancer Hospital; Baylor College of Medicine; Beckman Research Institute of City of Hope; Buck Institute for Research on Aging; Canada's Michael Smith Genome Sciences Centre; Harvard Medical School; Helen F. Graham Cancer Center & Research Institute at Christiana Care Health Services et al, . Integrated genomic and molecular characterization of cervical cancer. Nature. 543:378–384. 2017. View Article : Google Scholar : PubMed/NCBI
27	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
28	Zhang Y, Wang D, Wu D, Zhang D and Sun M: Long noncoding RNA KCNMB2-AS1 stabilized by N⁶-methyladenosine modification promotes cervical cancer growth through acting as a competing endogenous RNA. Cell Transplant. 29:9636897209643822020. View Article : Google Scholar : PubMed/NCBI
29	Min H and He W: Long non-coding RNA ARAP1-AS1 promotes the proliferation and migration in cervical cancer through epigenetic regulation of DUSP5. Cancer Biol Ther. 21:907–914. 2020. View Article : Google Scholar : PubMed/NCBI
30	Wang AH, Zhao JM, Du J, Pang QX and Wang MQ: Long noncoding RNA LUCAT1 promotes cervical cancer cell proliferation and invasion by upregulating MTA1. Eur Rev Med Pharmacol Sci. 24:86232020.PubMed/NCBI
31	Taheri M and Ghafouri-Fard S: Long Non-coding RNA signature in cervical cancer. Klin Onkol. 31:403–408. 2018. View Article : Google Scholar : PubMed/NCBI
32	Bu D, Yu K, Sun S, Xie C, Skogerbø G, Miao R, Xiao H, Liao Q, Luo H, Zhao G, et al: NONCODE v3.0: Integrative annotation of long noncoding RNAs. Nucleic Acids Res. 40:D210–D215. 2012. View Article : Google Scholar : PubMed/NCBI
33	Braga EA, Fridman MV, Moscovtsev AA, Filippova EA, Dmitriev AA and Kushlinskii NE: LncRNAs in ovarian cancer progression, metastasis, and main pathways: ceRNA and alternative mechanisms. Int J Mol Sci. 21:88552020. View Article : Google Scholar : PubMed/NCBI
34	Zheng D, Dai Y, Wang S and Xing X: MicroRNA-299-3p promotes the sensibility of lung cancer to doxorubicin through directly targeting ABCE1. Int J Clin Exp Pathol. 8:10072–10081. 2015.PubMed/NCBI
35	Wang JY, Jiang JB, Li Y, Wang YL and Dai Y: MicroRNA-299-3p suppresses proliferation and invasion by targeting VEGFA in human colon carcinoma. Biomed Pharmacother. 93:1047–1054. 2017. View Article : Google Scholar : PubMed/NCBI
36	Zhao R, Liu Q and Lou C: MicroRNA-299-3p regulates proliferation, migration and invasion of human ovarian cancer cells by modulating the expression of OCT4. Arch Biochem Biophys. 651:21–27. 2018. View Article : Google Scholar : PubMed/NCBI
37	Yu Y, Zhao JD and Yang H: MiR-299-3p inhibits proliferation and invasion of cervical cancer cell via targeting TCF4. Eur Rev Med Pharmacol Sci. 23:5621–5627. 2019.PubMed/NCBI
38	Li X, Ma N, Zhang Y, Wei H, Zhang H, Pang X, Li X, Wu D, Wang D, Yang Z and Zhang S: Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway. Cell Death Dis. 11:3992020. View Article : Google Scholar : PubMed/NCBI
39	Dong J, Sui L, Wang Q, Chen M and Sun H: MicroRNA-26a inhibits cell proliferation and invasion of cervical cancer cells by targeting protein tyrosine phosphatase type IVA 1. Mol Med Rep. 10:1426–1432. 2014. View Article : Google Scholar : PubMed/NCBI
40	Li C, Jiang Y, Miao R, Qu K, Zhang J and Liu C: MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition inhibitor in human HCC by targeting the PTP4A1/c-Src axis. Int J Oncol. 52:536–546. 2018.PubMed/NCBI