circ‑ACACA promotes proliferation, invasion, migration and glycolysis of cervical cancer cells by targeting the miR‑582‑5p/ERO1A signaling axis

Huang,Dandan; Li,Cuimei

doi:10.3892/ol.2021.13056

circ‑ACACA promotes proliferation, invasion, migration and glycolysis of cervical cancer cells by targeting the miR‑582‑5p/ERO1A signaling axis

Authors:
- Dandan Huang
- Cuimei Li
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Affiliations: Department of Gynecology and Obstetrics, Inner Mongolia Baogang Hospital (The Third Affiliated Hospital of Inner Mongolia Medical University), Baotou, Inner Mongolia Autonomous Region 014010, P.R. China, Department of Gynecology and Obstetrics, Xi'An Fifth Hospital, Xi'An, Shaanxi 710000, P.R. China
Published online on: September 17, 2021 https://doi.org/10.3892/ol.2021.13056
Article Number: 795
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Circular RNAs (circ) have been reported to serve crucial roles in the regulation of cancer occurrence and development. The present study aimed to investigate the role of circ‑acetyl‑CoA carboxylase α (ACACA) in the progression of cervical cancer (CC). The expression levels of circ‑ACACA in several CC cell lines were first determined using reverse transcription‑quantitative PCR. circ‑ACACA expression was subsequently knocked down to evaluate its effects on the viability, proliferation, apoptosis, invasion and migration of CC cells using MTT, colony formation, TUNEL, transwell and wound healing assays, respectively. ¹³C‑labeling of intracellular metabolites and analysis of glucose consumption and lactate production were performed to determine the levels of glycolysis. In addition, the expression levels of endoplasmic reticulum oxidoreductase 1α (ERO1α; ERO1A) and glycolysis‑related proteins were analyzed using western blotting. The binding interactions among circ‑ACACA, microRNA (miR)‑582‑5p and ERO1A were validated using dual‑luciferase reporter assays. Subsequently, rescue experiments were performed to determine the potential underlying mechanism by which circ‑ACACA affected CC cell functions. The results revealed that circ‑ACACA expression was significantly upregulated in CC cells and silencing of circ‑ACACA significantly reduced the proliferation, invasion and migration, and promoted the apoptosis of CC cells. Knockdown of circ‑ACACA markedly inhibited glycolysis in CC cells. However, the effects of silencing of circ‑ACACA on CC cells were reversed following transfection with the miR‑582‑5p inhibitor or pcDNA3.1‑ERO1A overexpression plasmid. In conclusion, to the best of our knowledge, the present study was the first to investigate the role of circ‑ACACA in CC progression. The results suggested that circ‑ACACA may promote CC tumorigenesis and glycolysis by targeting the miR‑582‑5p/ERO1A signaling axis. Therefore, circ‑ACACA may be a promising biomarker for CC diagnosis and treatment.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
2	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
3	Fan Y, Sheng W, Meng Y, Cao Y and Li R: LncRNA PTENP1 inhibits cervical cancer progression by suppressing miR-106b. Artif Cells Nanomed Biotechnol. 48:393–407. 2020. View Article : Google Scholar : PubMed/NCBI
4	Fader AN: Surgery in cervical cancer. N Engl J Med. 379:1955–1957. 2018. View Article : Google Scholar : PubMed/NCBI
5	Fan Y, Meng Y, Yang S, Wang L, Zhi W, Lazare C, Cao C and Wu P: Screening of cervical cancer with self-collected cervical samples and next-generation sequencing. Dis Markers. 2018:48265472018. View Article : Google Scholar : PubMed/NCBI
6	Wilusz JE and Sharp PA: Molecular biology. A circuitous route to noncoding RNA. Science. 340:440–441. 2013. View Article : Google Scholar : PubMed/NCBI
7	Jia YJ, Liu MJ and Wang SX: CircRNA hsa_circRNA_0001776 inhibits proliferation and promotes apoptosis in endometrial cancer via downregulating LRIG2 by sponging miR-182. Cancer Cell Int. 20:4122020. View Article : Google Scholar : PubMed/NCBI
8	Zhang W, Liu T, Li TS and Zhao XD: Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis. Cancer Gene Ther. 28:279–293. 2021. View Article : Google Scholar : PubMed/NCBI
9	Wu W, Xi W, Li H, Yang M and Yao X: Circular RNA circ-ACACA regulates proliferation, migration and glycolysis in non-small-cell lung carcinoma via miR-1183 and PI3K/PKB pathway. Int J Mol Med. 45:1814–1824. 2020.PubMed/NCBI
10	Liu J, Liu S, Deng X, Rao J, Huang K, Xu G and Wang X: MicroRNA-582-5p suppresses non-small cell lung cancer cells growth and invasion via downregulating NOTCH1. PLoS One. 14:e02176522019. View Article : Google Scholar : PubMed/NCBI
11	Huang S, Zou C, Tang Y, Wa Q, Peng X, Chen X, Yang C, Ren D, Huang Y, Liao Z, et al: miR-582-3p and miR-582-5p suppress prostate cancer metastasis to bone by repressing TGF-β signaling. Mol Ther Nucleic Acids. 16:91–104. 2019. View Article : Google Scholar : PubMed/NCBI
12	Wu J, Li W, Ning J, Yu W, Rao T and Cheng F: Long noncoding RNA UCA1 targets miR-582-5p and contributes to the progression and drug resistance of bladder cancer cells through ATG7-mediated autophagy inhibition. Onco Targets Ther. 12:495–508. 2019. View Article : Google Scholar : PubMed/NCBI
13	Li L and Ma L: Upregulation of miR-582-5p regulates cell proliferation and apoptosis by targeting AKT3 in human endometrial carcinoma. Saudi J Biol Sci. 25:965–970. 2018. View Article : Google Scholar : PubMed/NCBI
14	Zhang Y, Huang W, Ran Y, Xiong Y, Zhong Z, Fan X, Wang Z and Ye Q: miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3. Tumour Biol. 36:8309–8316. 2015. View Article : Google Scholar : PubMed/NCBI
15	Tanaka T, Kutomi G, Kajiwara T, Kukita K, Kochin V, Kanaseki T, Tsukahara T, Hirohashi Y, Torigoe T, Okamoto Y, et al: Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer. Oncotarget. 8:24706–24718. 2017. View Article : Google Scholar : PubMed/NCBI
16	Zhang J, Yang J, Lin C, Liu W, Huo Y, Yang M, Jiang SH, Sun Y and Hua R: Endoplasmic reticulum stress-dependent expression of ERO1L promotes aerobic glycolysis in pancreatic cancer. Theranostics. 10:8400–8414. 2020. View Article : Google Scholar : PubMed/NCBI
17	Han F, Xu Q, Zhao J, Xiong P and Liu J: ERO1L promotes pancreatic cancer cell progression through activating the Wnt/catenin pathway. J Cell Biochem. 119:8996–9005. 2018. View Article : Google Scholar : PubMed/NCBI
18	Yan W, Wang X, Liu T, Chen L, Han L, Xu J, Jin G, Harada K, Lin Z and Ren X: Expression of endoplasmic reticulum oxidoreductase 1-α in cholangiocarcinoma tissues and its effects on the proliferation and migration of cholangiocarcinoma cells. Cancer Manag Res. 11:6727–6739. 2019. View Article : Google Scholar : PubMed/NCBI
19	Zilli F, Marques Ramos P, Auf der Maur P, Jehanno C, Sethi A, Coissieux MM, Eichlisberger T, Sauteur L, Rouchon A, Bonapace L, et al: The NFIB-ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells. EMBO Mol Med. 13:e131622021. View Article : Google Scholar : PubMed/NCBI
20	Zhang Y, Li T, Zhang L, Shangguan F, Shi G, Wu X, Cui Y, Wang X, Wang X, Liu Y, et al: Targeting the functional interplay between endoplasmic reticulum oxidoreductin-1α and protein disulfide isomerase suppresses the progression of cervical cancer. EBioMedicine. 41:408–419. 2019. View Article : Google Scholar : PubMed/NCBI
21	Seol SY, Kim C, Lim JY, Yoon SO, Hong SW, Kim JW, Choi SH and Cho JY: Overexpression of Endoplasmic Reticulum Oxidoreductin 1-α (ERO1L) is associated with poor prognosis of gastric cancer. Cancer Res Treat. 48:1196–1209. 2016. View Article : Google Scholar : PubMed/NCBI
22	Takei N, Yoneda A, Sakai-Sawada K, Kosaka M, Minomi K and Tamura Y: Hypoxia-inducible ERO1α promotes cancer progression through modulation of integrin-β1 modification and signalling in HCT116 colorectal cancer cells. Sci Rep. 7:93892017. View Article : Google Scholar : PubMed/NCBI
23	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
24	Yamamoto T, Takano N, Ishiwata K, Ohmura M, Nagahata Y, Matsuura T, Kamata A, Sakamoto K, Nakanishi T, Kubo A, et al: Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway. Nat Commun. 5:34802014. View Article : Google Scholar : PubMed/NCBI
25	Guarnerio J, Zhang Y, Cheloni G, Panella R, Mae Katon J, Simpson M, Matsumoto A, Papa A, Loretelli C, Petri A, et al: Intragenic antagonistic roles of protein and circRNA in tumorigenesis. Cell Res. 29:628–640. 2019. View Article : Google Scholar : PubMed/NCBI
26	Zhang G, Liu Y, Yang J, Wang H and Xing Z: Inhibition of circ_0081234 reduces prostate cancer tumor growth and metastasis via miR-1/MAP3K1 axis. J Gene Med. e33762021.PubMed/NCBI
27	Yang C, Shi J, Wang J, Hao D, An J and Jiang J: Circ_0006988 promotes the proliferation, metastasis and angiogenesis of non-small cell lung cancer cells by modulating miR-491-5p/MAP3K3 axis. Cell Cycle. 20:1334–1346. 2021. View Article : Google Scholar : PubMed/NCBI
28	Wang J, Li S, Zhang G and Han H: Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622. J Biol Res (Thessalon). 28:142021. View Article : Google Scholar : PubMed/NCBI
29	Xie J, Chen Q, Zhou P and Fan W: Circular RNA hsa_circ_0000511 improves epithelial mesenchymal transition of cervical cancer by regulating hsa-mir-296-5p/HMGA1. J Immunol Res. 2021:99645382021. View Article : Google Scholar : PubMed/NCBI
30	Ding L, Zhao Y, Dang S, Wang Y, Li X, Yu X, Li Z, Wei J, Liu M and Li G: Circular RNA circ-DONSON facilitates gastric cancer growth and invasion via NURF complex dependent activation of transcription factor SOX4. Mol Cancer. 18:452019. View Article : Google Scholar : PubMed/NCBI
31	Li Y, Zheng F, Xiao X, Xie F, Tao D, Huang C, Liu D, Wang M, Wang L, Zeng F and Jiang G: CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 18:1646–1659. 2017. View Article : Google Scholar : PubMed/NCBI
32	Pelicano H, Martin DS, Xu RH and Huang P: Glycolysis inhibition for anticancer treatment. Oncogene. 25:4633–4646. 2006. View Article : Google Scholar : PubMed/NCBI
33	Hua Q, Mi BM, Xu F, Wen J, Zhao L, Liu J and Huang G: Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1α axis. Theranostics. 10:4762–4778. 2020. View Article : Google Scholar : PubMed/NCBI
34	Sun SF, Li WW, Ma XM and Luan H: Long noncoding RNA LINC00265 promotes glycolysis and lactate production of colorectal cancer through regulating of miR-216b-5p/TRIM44 axis. Digestion. 101:391–400. 2020. View Article : Google Scholar : PubMed/NCBI
35	Shang RZ, Wang M, Dai B, Du J, Wang J, Liu Z, Qu S, Yang X, Liu J, Xia C, et al: Long noncoding RNA SLC2A1-AS1 regulates aerobic glycolysis and progression in hepatocellular carcinoma via inhibiting the STAT3/FOXM1/GLUT1 pathway. Mol Oncol. 14:1381–1396. 2020. View Article : Google Scholar : PubMed/NCBI
36	Xu J, Tan QQ and Lie T: USP22 promotes the expression of GLUT1 and HK2 to facilitate growth and glycolysis in cervical cancer cells. Eur J Gynaecol Oncol. 41:790–796. 2020. View Article : Google Scholar
37	Yeung C, Gibson AE, Issaq SH, Oshima N, Baumgart JT, Edessa LD, Rai G, Urban DJ, Johnson MS, Benavides GA, et al: Targeting glycolysis through inhibition of lactate dehydrogenase impairs tumor growth in preclinical models of ewing sarcoma. Cancer Res. 79:5060–5073. 2019. View Article : Google Scholar : PubMed/NCBI
38	Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfør K, Rofstad EK and Mueller-Klieser W: High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res. 60:916–921. 2000.PubMed/NCBI
39	Wang M, Wang W, Wang J and Zhang J: MiR-182 promotes glucose metabolism by upregulating hypoxia-inducible factor 1α in NSCLC cells. Biochem Biophys Res Commun. 504:400–405. 2018. View Article : Google Scholar : PubMed/NCBI
40	Kristensen LS, Hansen TB, Veno MT and Kjems J: Circular RNAs in cancer: Opportunities and challenges in the field. Oncogene. 37:555–565. 2018. View Article : Google Scholar : PubMed/NCBI
41	Rupaimoole R, Calin GA, Lopez-Berestein G and Sood AK: miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 6:235–246. 2016. View Article : Google Scholar : PubMed/NCBI
42	Tian Y, Guan Y, Su Y, Luo W, Yang G and Zhang Y: MiR-582-5p inhibits bladder cancer-genesis by suppressing TTK Expression. Cancer Manag Res. 12:11933–11944. 2020. View Article : Google Scholar : PubMed/NCBI
43	Tang W, Ji M, He G, Yang L, Niu Z, Jian M, Wei Y, Ren L and Xu J: Silencing CDR1as inhibits colorectal cancer progression through regulating microRNA-7. Onco Targets Ther. 10:2045–2056. 2017. View Article : Google Scholar : PubMed/NCBI
44	Takei N, Yoneda A, Kosaka M, Sakai-Sawada K and Tamura Y: ERO1α is a novel endogenous marker of hypoxia in human cancer cell lines. BMC Cancer. 19:5102019. View Article : Google Scholar : PubMed/NCBI