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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Fluorescence in Situ Hybridization | Primary research

CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458

Authors: Yongyong Yan, Jiantian Yang, Janak L. Pathak, Haiyan Wang, Jun Zha, Yongxiang Wei, Haibo Tang, Linhu Ge

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Lung adenocarcinoma is metastatic cancer with a high mortality rate. Circular RNAs (circRNAs) are a type of noncoding RNA and play a vital role in cancer progression. However, the expression and function of circRNAs in lung adenocarcinoma are still mostly unknown.

Methods

In this study, we screened the differential expression of circRNAs in human bronchial epithelial cells (HBE) and A549 human lung adenocarcinoma cell line (A549) by human circRNA microarray and RT-qPCR. The role of overexpressed circRNA_104889 in A549 cell proliferation, apoptosis, migration, and invasion was studied extensively. Intracellular localization of circRNA_104889 was visualized by FISH assay. MiRNA sponging, ERK1/2 signaling, and caspase-3 expression were analyzed in siRNA-mediated circRNA_104889 knockdowned A549 cells.

Results

CircRNA microarray showed overexpression of circRNA_104889 (> 13-fold) in A459 cells compared to HBE. This finding was further corroborated by the RT-qPCR result. CircRNA_104889 was mainly localized in the cytoplasm of A549 cells. The knockdown of circRNA_104889 in A549 cells by si-RNA mediated RNA interference did not affect cell proliferation and apoptosis but significantly inhibited cell migration and invasion in vitro. Furthermore, knockdown of circRNA_104889 led to an increase of miR4458 expression. Overexpression of miR4458 inhibited A549 cell migration. Both the knockdown of circRNA_104889 and overexpression of miR4458 inhibited the caspase-3 expression and ERK1/2 phosphorylation in A549 cells.

Conclusions

CircRNA_104889 promotes lung adenocarcinoma cell migration and invasion by sponging miR4458 and targeting ERK1/2 signaling and caspase-3 expression.
Appendix
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Literature
1.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.PubMedCrossRef
2.
3.
4.
Williams CD, Gajra A, Ganti AK, Kelley MJ. Use and impact of adjuvant chemotherapy in patients with resected non-small cell lung cancer. Cancer Am Cancer Soc. 2014;120(13):1939–47.
5.
AbouHaidar MG, Venkataraman S, Golshani A, Liu B, Ahmad T. Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt. Proc Natl Acad Sci USA. 2014;111(40):14542–7.PubMedCrossRefPubMedCentral
6.
Haimovich G, Medina DA, Causse SZ, Garber M, Millan-Zambrano G, Barkai O, et al. Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis. Cell. 2013;153(5):1000–11.PubMedCrossRef
7.
Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015;10(2):170–7.PubMedCrossRef
8.
9.
10.
Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–8.PubMedCrossRef
11.
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20.PubMedCrossRef
12.
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.PubMedCrossRef
13.
Rong DW, Tang WW, Li ZX, Zhou J, Shi JF, Wang HJ, et al. Novel insights into circular RNAs in clinical application of carcinomas. Oncotargets Ther. 2017;10:2183–8.CrossRef
14.
Kristensen LS, Hansen TB, Veno MT, Kjems J. Circular RNAs in cancer: opportunities and challenges in the field. Oncogene. 2018;37(5):555–65.PubMedCrossRef
15.
Han JQ, Zhao GB, Ma X, Dong Q, Zhang H, Wang Y, et al. CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression. Biochem Biophys Res Co. 2018;503(4):2429–35.CrossRef
16.
Fan HQ, Li YY, Liu CD, Liu YM, Bai J, Li W. Circular RNA-100290 promotes cell proliferation and inhibits apoptosis in acute myeloid leukemia cells via sponging miR-203. Biochem Biophys Res Co. 2018;507(1–4):178–84.CrossRef
17.
Yao JT, Zhao SH, Liu QP, Lv MQ, Zhou DX, Liao ZJ, et al. Over-expression of CircRNA_100876 in non-small cell lung cancer and its prognostic value. Pathol Res Pract. 2017;213(5):453–6.PubMedCrossRef
18.
Chang H, Qu J, Wang J, Liang X, Sun W. Circular RNA circ_0026134 regulates non-small cell lung cancer cell proliferation and invasion via sponging miR-1256 and miR-1287. Biomed Pharmacother. 2019;112:108743.PubMedCrossRef
19.
Cui R, Kim T, Fassan M, Meng W, Sun HL, Jeon YJ, et al. MicroRNA-224 is implicated in lung cancer pathogenesis through targeting caspase-3 and caspase-7. Oncotarget. 2015;6(26):21802–15.PubMedPubMedCentralCrossRef
20.
Zhou M, Liu XJ, Li ZH, Huang Q, Li F, Li CY. Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells. Int J Cancer. 2018;143(4):921–30.PubMedPubMedCentralCrossRef
21.
Yang ZZ, Xie L, Han L, Qu X, Yang YH, Zhang Y, et al. Circular RNAs: regulators of cancer-related signaling pathways and potential diagnostic biomarkers for human cancers. Theranostics. 2017;7(12):3106–17.PubMedPubMedCentralCrossRef
22.
Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2015;43(Database issue):D146–52.PubMedCrossRef
23.
Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42(Database issue):D92–7.PubMedCrossRef
24.
Irizar H, Munoz-Culla M, Saenz-Cuesta M, Osorio-Querejeta I, Sepulveda L, Castillo-Trivino T, et al. Identification of ncRNAs as potential therapeutic targets in multiple sclerosis through differential ncRNA–mRNA network analysis. BMC Genomics. 2015;16:250.PubMedPubMedCentralCrossRef
25.
Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell. 2011;147(4):773–88.PubMedPubMedCentralCrossRef
26.
Wang YH, Yu XH, Luo SS, Han H. Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing. Immun Ageing. 2015;12:17.PubMedPubMedCentralCrossRef
27.
Zheng C, Niu H, Li M, Zhang H, Yang Z, Tian L, et al. Cyclic RNA hsacirc000595 regulates apoptosis of aortic smooth muscle cells. Mol Med Rep. 2015;12(5):6656–62.PubMedPubMedCentralCrossRef
28.
Liu Q, Zhang X, Hu X, Dai L, Fu X, Zhang J, et al. Circular RNA related to the Chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 ‘sponge’ in human cartilage degradation. Sci Rep. 2016;6:22572.PubMedPubMedCentralCrossRef
29.
Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu JZ, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141–57.PubMedPubMedCentralCrossRef
30.
Jiang M, Lash GE, Zhao XQ, Long Y, Guo CJ, Yang HL. CircRNA-0004904, CircRNA-0001855, and PAPP-A: potential novel biomarkers for the prediction of preeclampsia. Cell Physiol Biochem. 2018;46(6):2576–86.PubMedCrossRef
31.
Xander P, Brito RR, Perez EC, Pozzibon JM, de Souza CF, Pellegrino R, et al. Crosstalk between B16 melanoma cells and B-1 lymphocytes induces global changes in tumor cell gene expression. Immunobiology. 2013;218(10):1293–303.PubMedCrossRef
32.
Ai X, Wu Y, Zhang W, Zhang Z, Jin G, Zhao J, et al. Targeting the ERK pathway reduces liver metastasis of Smad4-inactivated colorectal cancer. Cancer Biol Ther. 2013;14(11):1059–67.PubMedPubMedCentralCrossRef
33.
Gao J, Liu X, Yang F, Liu T, Yan Q, Yang X. By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis. Oncotarget. 2015;6(29):27187–98.PubMedPubMedCentralCrossRef
34.
Ha GH, Park JS, Breuer EK. TACC3 promotes epithelial-mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways. Cancer Lett. 2013;332(1):63–73.PubMedCrossRef
35.
Miao JH, Wang SQ, Zhang MH, Yu FB, Zhang L, Yu ZX, et al. Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK pathway. Oncol Rep. 2014;32(4):1497–504.PubMedCrossRef
36.
Wu S, Lao XY, Sun TT, Ren LL, Kong X, Wang JL, et al. Knockdown of ZFX inhibits gastric cancer cell growth in vitro and in vivo via downregulating the ERK-MAPK pathway. Cancer Lett. 2013;337(2):293–300.PubMedCrossRef
37.
Yang D, Wang LL, Dong TT, Shen YH, Guo XS, Liu CY, et al. Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2/Akt and ERK signaling pathways. Am J Cancer Res. 2015;5(10):3085–97.PubMedPubMedCentral
38.
Zeng Z, Leng T, Feng X, Sun H, Inoue K, Zhu L, et al. Silencing TRPM7 in mouse cortical astrocytes impairs cell proliferation and migration via ERK and JNK signaling pathways. PLoS ONE. 2015;10(3):e0119912.PubMedPubMedCentralCrossRef
39.
Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J Biol Chem. 2009;284(9):5731–41.PubMedCrossRef
40.
Tang D, Sun B, Yu H, Yang Z, Zhu L. Tumor-suppressing effect of miR-4458 on human hepatocellular carcinoma. Cell Physiol Biochem. 2015;35(5):1797–807.PubMedCrossRef
41.
Qin Y, Cheng C, Lu H, Wang Y. miR-4458 suppresses glycolysis and lactate production by directly targeting hexokinase2 in colon cancer cells. Biochem Biophys Res Commun. 2016;469(1):37–43.PubMedCrossRef
42.
Ding D, Qi W, Yu D, Jiang H, Han C, Kim MJ, et al. Addition of exogenous NAD + prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures. PLoS ONE. 2013;8(11):e79817.PubMedPubMedCentralCrossRef
43.
Mai L, Yi F, Gou X, Zhang J, Wang C, Liu G, et al. The overexpression of MCPH1 inhibits cell growth through regulating cell cycle-related proteins and activating cytochrome c-caspase 3 signaling in cervical cancer. Mol Cell Biochem. 2014;392(1–2):95–107.PubMedCrossRef
44.
Tourigny A, Charbonneau F, Xing P, Boukrab R, Rousseau G, St-Arnaud R, et al. CYP24A1 exacerbated activity during diabetes contributes to kidney tubular apoptosis via caspase-3 increased expression and activation. PLoS ONE. 2012;7(10):e48652.PubMedPubMedCentralCrossRef
45.
Yu Z, Zhang C, Wang H, Xing J, Gong H, Yu E, et al. Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway. Cancer Lett. 2014;353(2):182–93.PubMedCrossRef
46.
Cheng YJ, Lee CH, Lin YP, Huang JY, Su CC, Chang WT, et al. Caspase-3 enhances lung metastasis and cell migration in a protease-independent mechanism through the ERK pathway. Int J Cancer. 2008;123(6):1278–85.PubMedCrossRef
47.
48.
Fang L, Du WW, Yang X, Chen K, Ghanekar A, Levy G, et al. Versican 3′-untranslated region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. FASEB J. 2013;27(3):907–19.PubMedCrossRef
49.
Lee DY, Jeyapalan Z, Fang L, Yang J, Zhang Y, Yee AY, et al. Expression of versican 3′-untranslated region modulates endogenous microRNA functions. PLoS ONE. 2010;5(10):e13599.PubMedPubMedCentralCrossRef
50.
Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, et al. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011;147(2):370–81.PubMedPubMedCentralCrossRef
51.
Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, et al. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011;147(2):344–57.PubMedPubMedCentralCrossRef
52.
Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38(16):5366–83.PubMedPubMedCentralCrossRef
53.
Wang L, Guo ZY, Zhang R, Xin B, Chen R, Zhao J, et al. Pseudogene OCT4-pg4 functions as a natural micro RNA sponge to regulate OCT4 expression by competing for miR-145 in hepatocellular carcinoma. Carcinogenesis. 2013;34(8):1773–81.PubMedCrossRef
Metadata
Title
CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458
Authors
Yongyong Yan
Jiantian Yang
Janak L. Pathak
Haiyan Wang
Jun Zha
Yongxiang Wei
Haibo Tang
Linhu Ge
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01522-2

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