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hsa_circ_0000218/hsa-miR-139-3p/SOX4 regulatory feedback circuit influences the proliferation and apoptosis of gastric cancer cells

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Abstract

Previous studies have reported that circular (circ)RNAs serve an important role in cancer progression, but the effects of hsa_circRNA_0000218 (circ_0000218) and its potential underlying mechanism in gastric cancer (GC) are not completely understood. In the present study, dual luciferase reporter and RNA pull down assays were performed to detect the relationship between microRNA (miR)-139-3p and circ_0000218, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect circ_0000218, miR-139-3p and SRY-box transcription factor 4 (SOX4) mRNA expression levels in GC and GES-1 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Western blotting was performed to assess cleaved-Caspase3 and Caspase3 expression levels in GC cells. circ_0000218 and SOX4 were highly expressed, whereas miR-139-3p was lowly expressed in GC cells. Moreover, circ_0000218 negatively regulated miR-139-3p in GC cells. circ_0000218 knockdown inhibited GC cell proliferation, promoted apoptosis and enhanced cleaved-Caspase3 expression in GC cells, whereas miR-139-3p knockdown reversed these effects. miR-139-3p overexpression inhibited proliferation and induced apoptosis in GC cells, but these effects were reversed by SOX4 overexpression. Collectively, the present study demonstrated that circ_0000218 upregulated SOX4 via downregulating miR-139-3p to promote GC progression.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Bai Y, Hou J, Wang X, Geng L, Jia X, Xiang L, Nan K (2020) Circ_0000218 plays a carcinogenic role in laryngeal cancer through regulating microRNA-139-3p/Smad3 axis. Pathol Res Pract 216:103

    Article  Google Scholar 

  • Chen J, Ju HL, Yuan XY, Wang TJ, Lai BQ (2016) SOX4 is a potential prognostic factor in human cancers: a systematic review and meta-analysis. Clin Transl Oncol 18:65–72

    Article  CAS  Google Scholar 

  • Chen J, Li Y, Chen B, He J, Chen B, Lyu D, Zheng B, Xu Y, Long Z, Zhou Y, Zhu H, Wang Y, He X, Shi Y, Huang S (2017) Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer Lett 388:208–219

    Article  CAS  Google Scholar 

  • Denzler R, Mcgeary SE, Title AC, Agarwal V, Bartel DP, Stoffel M (2016) Impact of microRNA levels, target-site complementarity, and cooperativity on competing endogenous rna-regulated gene expression. Mol Cell 64:565–579

    Article  CAS  Google Scholar 

  • Fang CL, Hseu YC, Lin YF, Hung ST, Tai C, Uen YH, Lin KY (2012) Clinical and prognostic association of transcription factor SOX4 in gastric cancer. PLoS ONE 7:e52804

    Article  CAS  Google Scholar 

  • Geng Y, Zheng X, Hu W, Wang Q, Xu Y, He W, Wu C, Zhu D, Wu C, Jiang J (2019) Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression. Clin Sci 133:1197–1213

    Article  CAS  Google Scholar 

  • Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388

    Article  CAS  Google Scholar 

  • Li P, Chen S, Chen H, Mo X, Li T, Shao Y, Xiao B, Guo J (2015) Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta 444:132–136

    Article  CAS  Google Scholar 

  • Li D, Liu J, Guo B, Liang C, Dang L, Lu C, He XJ, Cheung HY, Xu L, Lu CW, He B, Liu B, Shaikh AB, Li FF, Wang LY, Yang ZJ, Ting ADW, Peng SL, Zhang ZK, Zhang BT, Pan XH, Qian A, Shang P, Xiao LB, Jiang BH, Wong CK, Xu JK, Bian ZX, Liang ZC, Guo DA, Zhu HL, Tan WH, Lu AP, Zhang G (2016) Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 7:10872

    Article  CAS  Google Scholar 

  • Liang M, Liu ZY, Lin H, Shi BY, Li M, Chen T, Qin LY, Niu QL, Yu GF, Jiang H, Zhou XK (2019) High-throughput sequencing reveals circular RNA hsa_circ_0000592 as a novel player in the carcinogenesis of gastric carcinoma. Biosci Rep 39:BSR20181900

    Article  CAS  Google Scholar 

  • Liao YL, Sun YM, Chau GY, Chau YP, Lai TC, Wang JL, Horng JT, Hsiao M, Tsou AP (2008) Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma. Oncogene 27:5578–5589

    Article  CAS  Google Scholar 

  • Liu R, Yang M, Meng YL, Liao J, Sheng JY, Pu YP, Yin LP, Sun JK (2013) Tumor-suppressive function of miR-139–5p in esophageal squamous cell carcinoma. PLoS ONE 8:e77068

    Article  CAS  Google Scholar 

  • Liu X, Duan B, Dong Y, He CZ, Zhou HM, Sheng HH, Gao HJ, Zhang XZ (2014) MicroRNA-139-3p indicates a poor prognosis of colon cancer. Int J Clin Exp Pathol 7:8046–8052

    PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Ma HQ, Saradhi M, Lu Y, Sun BH, Wang EZ, Leng XH, Gong Y, Shen HF, Yin CC, Jones D, Hesham MA, James YM, Patrick ZM, Ma YP, Hagop MK, Ralph BA, Armand G, Sun XP (2014) The Sox4/Tcf7l1 axis promotes progression of BCR-ABL-positive acute lymphoblastic leukemia. Haematologica 99:1591–1598

    Article  CAS  Google Scholar 

  • Mads A, Karin BD, Carsten W, Flemming BS, Thomas T, Guido S, Klaus MEJ, Lars D, Torben R (2006) SOX4 expression in bladder carcinoma: clinical aspects and in vitro functional characterization. Cancer Res 66(7):3434–3442

    Article  Google Scholar 

  • Nader O, Mei LM, Letetia J, Sabina S, Bin Y, Karen LH, Thelma RT, Michelle ML, David AL, Scott CK (2013) PML-RARα co-operates with Sox4 in acute myeloid leukemia development in mice. Haematologica 98:424–427

    Article  Google Scholar 

  • Narahari A, Hussain M, Sreeram V (2017) MicroRNAs as biomarkers for psychiatric condition: a review of current research. Innov Clin Neurosci 14:53–55

    PubMed  PubMed Central  Google Scholar 

  • Ng L, Wan TM, Man JH, Chow AK, Iyer D, Chen G, Yau TC, Lo OS, Foo DC, Poon JT, Leung WK, Pang RW, Law WL (2017) Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer. Oncotarget 8:27393–27400

    Article  Google Scholar 

  • Pei FL, Cao MZ, Li YF (2020) Circ_0000218 plays a carcinogenic role in colorectal cancer progression by regulating miR-139-3p/RAB1A axis. J Biochem 167:55–65

    Article  CAS  Google Scholar 

  • Poirier C, Desgagne V, Guerin R, Bouchard L (2017) MicroRNAs in pregnancy and gestational diabetes mellitus: Emerging role in maternal metabolic regulation. Curr Diab Rep 17:35

    Article  Google Scholar 

  • Prior HM, Walter MA (1996) SOX genes: architects of development. Mol Med 2:405–412

    Article  CAS  Google Scholar 

  • Rask L, Balslev E, Sckilde R, Høgdall E, Flyger H, Eriksen J, Litman T (2014) Differential expression of MiR-139, miR-486 and miR-2l in breast cancer patients sub-classifted according to lymph node status. Cell Oncol (dordr) 37(3):215–227

    Article  CAS  Google Scholar 

  • Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO (2012) Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS ONE 7:e30733

    Article  CAS  Google Scholar 

  • Shen K, Mao R, Ma L, Li YQ, Qiu YY, Cui DL, Le V, Yin PH, Ni L, Liu JW (2014) Post-transcriptional regulation of the tumor suppressor miR-139-5p and a network of miR-139-5p-mediated mRNA interactions in colorectal cancer. FEBS J 281(16):3609–3624

    Article  CAS  Google Scholar 

  • Song MX, Yin Y, Zhang JW, Zhang BB, Bian ZH, Quan C, Zhou LY, Hu YL, Wang QF, Ni S, Fei BJ, Wang WL, Du X, Hua D, Huang ZH (2014) MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1. Protein Cell 5(11):851–861

    Article  CAS  Google Scholar 

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics. CA Cancer J Clin 65:87–108

    Article  Google Scholar 

  • Wu W, Yong WW, Chung MC (2016) A simple biomarker scoring matrix for early gastric cancer detection. Proteomics 16:2921–2930

    Article  CAS  Google Scholar 

  • Xia T, Liao Q, Jiang X, Shao YF, Xiao BX, Xi Y, Guo JM (2014) Long noneoding RNA associated-competing endogenous RNAs in gastric cancer. Sci Rep 4:6088

    Article  CAS  Google Scholar 

  • Yang Y, Gao M, Li Y, Li M, Ma Q (2020) LncRNA CTBP1-AS2 facilitates gastric cancer progression via regulating the miR-139-3p/MMP11 axis. Onco Targets Ther 13:11537–11547

    Article  CAS  Google Scholar 

  • Yonemori M, Seke N, Yoshino H, Matsushita R, Miyamoto K, Nakagawa M, Enokida H (2016) Dual tumor-suppressors miR-139-5p and miR-139-3p targetingmatrix metalloprotease 11 in bladder cancer. Cancer Sci 107:1233–1242

    Article  CAS  Google Scholar 

  • Yu X, Odenthal M, Fries JW (2016) Exosomes as miRNA carriers: formation-function-future. Int J Mol Sci 17:2028–2040

    Article  Google Scholar 

  • Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, Sun H, Pan Y, He B (2018) Wang S CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis 9:417

    Article  Google Scholar 

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Author notes

  1. Ganlin Xia and Anxin Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Wuhan Puren Hospital, Wuhan, 430080, China

    Ganlin Xia & Anxin Wang

  2. Department of Vascular Surgery, Wuhan Puren Hospital, No. 1 Benxi Street, Qingshan District, Wuhan, 430080, China

    Liangxue Li

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  1. Ganlin Xia
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  2. Anxin Wang
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Correspondence to Liangxue Li.

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Xia, G., Wang, A. & Li, L. hsa_circ_0000218/hsa-miR-139-3p/SOX4 regulatory feedback circuit influences the proliferation and apoptosis of gastric cancer cells. Cytotechnology 74, 89–98 (2022). https://doi.org/10.1007/s10616-021-00509-9

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  • DOI: https://doi.org/10.1007/s10616-021-00509-9

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