MicroRNA‑130a‑3p inhibition suppresses cervical cancer cell progression

Causin,Rhafaela Lima; Causin,Rhafaela Lima; Van Helvoort Lengert,André; Van Helvoort Lengert,André; Gomes,Izabela Natalia Faria; Gomes,Izabela Natalia Faria; De Freitas,Ana Julia Aguiar; De Freitas,Ana Julia Aguiar; Rosa,Marcela Nunes; Rosa,Marcela Nunes; Dos Reis,Ricardo; Dos Reis,Ricardo; Reis,Rui Manuel; Reis,Rui Manuel; Marques,Márcia Maria Chiquitelli; Marques,Márcia Maria Chiquitelli

doi:10.3892/or.2023.8546

MicroRNA‑130a‑3p inhibition suppresses cervical cancer cell progression

Authors:
- Rhafaela Lima Causin
- André Van Helvoort Lengert
- Izabela Natalia Faria Gomes
- Ana Julia Aguiar De Freitas
- Marcela Nunes Rosa
- Ricardo Dos Reis
- Rui Manuel Reis
- Márcia Maria Chiquitelli Marques
View Affiliations

Affiliations: Molecular Oncology Research Center, Barretos Cancer Hospital, Teaching and Research Institute, Barretos, São Paulo 14784-400, Brazil, Molecular Oncology Research Center, Barretos Cancer Hospital, Teaching and Research Institute, Barretos, São Paulo 14784‑400, Brazil, Department of Gynecological Oncology, Barretos Cancer Hospital, Barretos, São Paulo 14784-400, Brazil
Published online on: April 13, 2023 https://doi.org/10.3892/or.2023.8546
Article Number: 109
Copyright: © Causin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs or miRs) play essential roles in the initiation and progression of human tumors, including cervical cancer. However, the mechanisms underlying their actions in cervical cancer remain unclear. The present study aimed to evaluate the functional role of miR‑130a‑3p in cervical cancer. Cervical cancer cells were transfected with a miRNA inhibitor (anti‑miR‑130a‑3p) and a negative control. Adhesion‑independent cell proliferation, migration and invasion were evaluated. The findings presented herein demonstrated that miR‑130a‑3p was overexpressed in HeLa, SiHa, CaSki, C‑4I and HCB‑514 cervical cancer cells. The inhibition of miR‑130a‑3p significantly reduced the proliferation, migration and invasion of cervical cancer cells. The canonical delta‑like Notch1 ligand (DLL1) was identified as a possible direct target of miR‑103a‑3p. The DLL1 gene was further found to be significantly downregulated in cervical cancer tissues. On the whole, the present study demonstrates that miR‑130a‑3p contributes to the proliferation, migration and invasion of cervical cancer cells. Therefore, miR‑130a‑3p may be used as a biomarker to determine cervical cancer progression.

View Figures

View References

1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
2	Espenel S, Garcia MA, Trone JC, Guillaume E, Harris A, Rehailia-Blanchard A, He MY, Ouni S, Vallard A, Rancoule C, et al: From IB2 to IIIB locally advanced cervical cancers: report of a ten-year experience. Radiat Oncol. 13:162018. View Article : Google Scholar : PubMed/NCBI
3	Robin TP, Amini A, Schefter TE, Behbakht K and Fisher CM: Disparities in standard of care treatment and associated survival decrement in patients with locally advanced cervical cancer. Gynecol Oncol. 143:319–325. 2016. View Article : Google Scholar : PubMed/NCBI
4	Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, Chon HS, Chu C, Clark R, Cohn D, et al: Cervical cancer, Version 3.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 17:64–84. 2019. View Article : Google Scholar : PubMed/NCBI
5	He Y, Han SB, Liu Y, Zhang JJ and Wu YM: Role of APOA1 in the resistance to platinum-based chemotherapy in squamous cervical cancer. BMC Cancer. 22:4112022. View Article : Google Scholar : PubMed/NCBI
6	International Agency for Research on Cancer I, organizador, . IARC monographs on the evaluation of carcinogenic risks to humans. 90. Human papillomaviruses: This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans which met in Lyon, 15–22 February 2005. IARC; Lyon: pp. pp6702007
7	Da Silva MLR, De Albuquerque BHDR, Allyrio TADMF, De Almeida VD, Cobucci RNDO, Bezerra FL, Andrade VS, Lanza DCF, De Azevedo JCV, De Araújo JMG and Fernandes JV: The role of HPV-induced epigenetic changes in cervical carcinogenesis (Review). Biomed Rep. 15:602021. View Article : Google Scholar : PubMed/NCBI
8	Hanahan D: Hallmarks of Cancer: New dimensions. Cancer Discov. 12:31–46. 2022. View Article : Google Scholar : PubMed/NCBI
9	Wang J and Chen L: The role of miRNAs in the invasion and metastasis of cervical cancer. Biosci Rep. 39:BSR201813772019. View Article : Google Scholar : PubMed/NCBI
10	Gao C, Zhou C, Zhuang J, Liu L, Liu C, Li H, Liu G, Wei J and Sun C: MicroRNA expression in cervical cancer: Novel diagnostic and prognostic biomarkers. J Cell Biochem. 119:7080–7090. 2018. View Article : Google Scholar : PubMed/NCBI
11	Siomi H and Siomi MC: Posttranscriptional regulation of microRNA biogenesis in animals. Mol Cell. 38:323–332. 2010. View Article : Google Scholar : PubMed/NCBI
12	Ardekani AM and Naeini MM: The Role of MicroRNAs in human diseases. Avicenna J Med Biotechnol. 2:161–179. 2010.PubMed/NCBI
13	Causin RL, de Freitas AJA, Trovo Hidalgo Filho CM, dos Reis R, Reis RM and Marques MMC: A systematic review of MicroRNAs involved in cervical cancer progression. Cells. 10:6682021. View Article : Google Scholar : PubMed/NCBI
14	Kovall RA, Gebelein B, Sprinzak D and Kopan R: The canonical notch signaling pathway: Structural and biochemical insights into shape, sugar, and force. Dev Cell. 41:228–241. 2017. View Article : Google Scholar : PubMed/NCBI
15	Bray SJ: Notch signalling in context. Nat Rev Mol Cell Biol. 17:722–735. 2016. View Article : Google Scholar : PubMed/NCBI
16	Penton AL, Leonard LD and Spinner NB: Notch signaling in human development and disease. Semin Cell Dev Biol. 23:450–457. 2012. View Article : Google Scholar : PubMed/NCBI
17	Capaccione KM and Pine SR: The Notch signaling pathway as a mediator of tumor survival. Carcinogenesis. 34:1420–1430. 2013. View Article : Google Scholar : PubMed/NCBI
18	Briot A and Iruela-Arispe ML: Blockade of specific NOTCH ligands: A new promising approach in cancer therapy. Cancer Discov. 5:112–114. 2015. View Article : Google Scholar : PubMed/NCBI
19	Khelil M, Griffin H, Bleeker MCG, Steenbergen RDM, Zheng K, Saunders-Wood T, Samuels S, Rotman J, Vos W, van den Akker BE, et al: Delta-like ligand-notch1 signaling is selectively modulated by HPV16 E6 to promote squamous cell proliferation and correlates with cervical cancer prognosis. Cancer Res. 81:1909–1921. 2021. View Article : Google Scholar : PubMed/NCBI
20	Causin RL, da Silva LS, Evangelista AF, Leal LF, Souza KCB, Pessôa-Pereira D, Matsushita GM, Reis RM, Fregnani JHTG and Marques MMC: MicroRNA biomarkers of high-grade cervical intraepithelial neoplasia in liquid biopsy. Biomed Res Int. 2021:66509662021. View Article : Google Scholar : PubMed/NCBI
21	He L, Wang HY, Zhang L, Huang L, Li JD, Xiong Y, Zhang MY, Jia WH, Yun JP, Luo RZ and Zheng M: Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer. Cell Death Dis. 5:e1205. 2014. View Article : Google Scholar : PubMed/NCBI
22	Fan Q, Huang T, Sun X, Yang X, Wang J, Liu Y, Ni T, Gu S, Li Y and Wang Y: miR-130a-3p promotes cell proliferation and invasion by targeting estrogen receptor α and androgen receptor in cervical cancer. Exp Ther Med. 21:4142021. View Article : Google Scholar : PubMed/NCBI
23	Rosa MN, Evangelista AF, Leal LF, De Oliveira CM, Silva VAO, Munari CC, Munari FF, Matsushita GM, Dos Reis R, Andrade CE, et al: Establishment, molecular and biological characterization of HCB-514: A novel human cervical cancer cell line. Sci Rep. 9:19132019. View Article : Google Scholar : PubMed/NCBI
24	Silva-Oliveira RJ, Silva VAO, Martinho O, Cruvinel-Carloni A, Melendez ME, Rosa MN, de Paula FE, de Souza Viana L, Carvalho AL and Reis RM: Cytotoxicity of allitinib, an irreversible anti-EGFR agent, in a large panel of human cancer-derived cell lines: KRAS mutation status as a predictive biomarker. Cell Oncol (Dordr). 39:253–263. 2016. View Article : Google Scholar : PubMed/NCBI
25	miRCURY LNA miRNA Inhibitors and Power Inhibitors. [Citado 9 de fevereiro de 2023]. Disponível em. https://www.qiagen.com/us/products/discovery-and-translational-research/functional-and-cell-analysis/mirna-functional-anal-sis/mircury-lna-mirna-inhibitors/mircury-lna-mirna-inhibitors?catno=339126
26	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
27	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
28	Causin RL, Pessôa-Pereira D, Souza KCB, Evangelista AF, Reis RMV, Fregnani JHTG and Marques MMC: Identification and performance evaluation of housekeeping genes for microRNA expression normalization by reverse transcription-quantitative PCR using liquid-based cervical cytology samples. Oncol Lett. 18:4753–4761. 2019.PubMed/NCBI
29	Geissmann Q: OpenCFU, a new free and open-source software to count cell colonies and other circular objects. PLoS One. 8:e540722013. View Article : Google Scholar : PubMed/NCBI
30	Hu Y, Sun X, Mao C, Guo G, Ye S, Xu J, Zou R, Chen J, Wang L, Duan P and Xue X: Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration. Cancer Med. 6:471–482. 2017. View Article : Google Scholar : PubMed/NCBI
31	Yew TL, Hung YT, Li HY, Chen HW, Chen LL, Tsai KS, Chiou SH, Chao KC, Huang TF, Chen HL and Hung SC: Enhancement of wound healing by human multipotent stromal cell conditioned medium: The paracrine factors and p38 MAPK activation. Cell Transplant. 20:693–706. 2011. View Article : Google Scholar : PubMed/NCBI
32	Martinho O, Silva-Oliveira R, Miranda-Gonçalves V, Clara C, Almeida JR, Carvalho AL, Barata JT and Reis RM: In vitro and in vivo analysis of RTK inhibitor efficacy and identification of its novel targets in glioblastomas. Transl Oncol. 6:187–196. 2013. View Article : Google Scholar : PubMed/NCBI
33	de Andrade DAP, da Silva LS, Laus AC, de Lima MA, Berardinelli GN, da Silva VD, Matsushita GM, Bonatelli M, da Silva ALV, Evangelista AF, et al: A 4-Gene signature associated with recurrence in low- and intermediate-risk endometrial cancer. Front Oncol. 11:7292192021. View Article : Google Scholar : PubMed/NCBI
34	Tokar T, Pastrello C, Rossos AEM, Abovsky M, Hauschild AC, Tsay M, Lu R and Jurisica I: mirDIP 4.1-integrative database of human microRNA target predictions. Nucleic Acids Res. 46:D360–D370. 2018. View Article : Google Scholar : PubMed/NCBI
35	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:e050052015. View Article : Google Scholar : PubMed/NCBI
36	Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. View Article : Google Scholar : PubMed/NCBI
37	Tang Z, Kang B, Li C, Chen T and Zhang Z: GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 47:W556–W560. 2019. View Article : Google Scholar : PubMed/NCBI
38	Park SJ, Yoon BH, Kim SK and Kim SY: GENT2: An updated gene expression database for normal and tumor tissues. BMC Medical Genomics. 12 (Suppl 5):S1012019. View Article : Google Scholar : PubMed/NCBI
39	Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–1550. 2005. View Article : Google Scholar : PubMed/NCBI
40	Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, et al: PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 34:267–273. 2003. View Article : Google Scholar : PubMed/NCBI
41	Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P and Mesirov JP: Molecular signatures database (MSigDB) 3.0. Bioinformatics. 27:1739–1740. 2011. View Article : Google Scholar : PubMed/NCBI
42	Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP and Tamayo P: The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 1:417–425. 2015. View Article : Google Scholar : PubMed/NCBI
43	da Zhang H, Jiang LH, Sun DW, Li J and Ji ZL: The role of miR-130a in cancer. Breast Cancer. 24:521–527. 2017. View Article : Google Scholar : PubMed/NCBI
44	Wang M, Wang X and Liu W: MicroRNA-130a-3p promotes the proliferation and inhibits the apoptosis of cervical cancer cells via negative regulation of RUNX3. Mol Med Rep. 22:2990–3000. 2020.PubMed/NCBI
45	Zhao X, Jin X, Zhang Q, Liu R, Luo H, Yang Z, Geng Y, Feng S, Li C, Wang L, et al: Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells. Cancer Cell Int. 21:6442021. View Article : Google Scholar : PubMed/NCBI
46	Hu W, Zheng X, Liu J, Zhang M, Liang Y and Song M: MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway. Bioengineered. 12:11634–1147. 2021. View Article : Google Scholar : PubMed/NCBI
47	Huang J, Zhao M, Hu H, Wang J, Ang L and Zheng L: MicroRNA-130a reduces drug resistance in breast cancer. Int J Clin Exp Pathol. 12:2699–2705. 2019.PubMed/NCBI
48	Liu Y, Li Y, Wang R, Qin S, Liu J, Su F, Yang Y, Zhao F, Wang Z and Wu Q: MiR-130a-3p regulates cell migration and invasion via inhibition of Smad4 in gemcitabine resistant hepatoma cells. J Exp Clin Cancer Res. 35:192016. View Article : Google Scholar : PubMed/NCBI
49	Yu F, Fan X, Chen B, Dong P and Zheng J: Activation of hepatic stellate cells is inhibited by microRNA-378a-3p via Wnt10a. Cell Physiol Biochem. 39:2409–2420. 2016. View Article : Google Scholar : PubMed/NCBI
50	Zhou H, Tang H, Li N, Chen H, Chen X, Gu L, Zhang L, Tian G and Tao D: MicroRNA-361-3p inhibit the progression of lymphoma by the Wnt/β-catenin signaling pathway. Cancer Manag Res. 12:12375–12384. 2020. View Article : Google Scholar : PubMed/NCBI