Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Gastric Cancer Growth Modulated by circSNTB2/miR-6938-5p/G0S2 and PDCD4

Author(s): Baohai Rong, Xiqi Chen, Guangdong Xie, Letian Han, Hanhan Chen, Qingying Sun* and Yongkun Zhou*

Volume 26, Issue 11, 2023

Published on: 30 December, 2022

Page: [1990 - 2002] Pages: 13

DOI: 10.2174/1386207326666221108112113

Price: $65

conference banner
Abstract

Background: Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Increasing studies have indicated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the precise mechanism and functions of most circRNAs are still unknown in gastric cancer.

Methods: In the present study, we aim to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. By analyzing the microarray data, we screened differential expressed circRNAs in the gastric cancer group and identified a down-regulated circRNA, hsa_circ_0040039 (circSNTB2). Mechanically, circSNTB2 served as a sponge for the miR-6938-5p and up-regulated its expression.

Results: Meanwhile, G0/G1 switch gene 2 (G0S2) and programmed cell death gene 4 (PDCD4) were identified to be the aim genes of miR-6938-5p, constructing circSNTB2/miR-6938-5p/G0S2 and PDCD4 pathways.

Conclusion: Taken together, our findings demonstrated that circSNTB2 plays an essential role in gastric cancer by regulating miR-6938-5p through G0S2 and PDCD4 genes. CircSNTB2 could be a promising biomarker for GC diagnosis and targeted therapy.

Graphical Abstract

[1]
Sitarz, R.; Skierucha, M.; Mielko, J.; Offerhaus, J.; Maciejewski, R.; Polkowski, W. Gastric cancer: Epidemiology, prevention, classification, and treatment. Cancer Manag. Res., 2018, 10, 239-248.
[http://dx.doi.org/10.2147/CMAR.S149619] [PMID: 29445300]
[2]
Feng, R.M.; Zong, Y.N.; Cao, S.M.; Xu, R.H. Current cancer situation in China: Good or bad news from the 2018 Global Cancer Statistics? Cancer Commun. (Lond.), 2019, 39(1), 22.
[http://dx.doi.org/10.1186/s40880-019-0368-6] [PMID: 31030667]
[3]
Tian, H.; Yang, W.; Hu, Y.; Liu, Z.; Chen, L.; Lei, L.; Zhang, F.; Cai, F.; Xu, H.; Liu, M.; Guo, C.; Chen, Y.; Xiao, P.; Chen, J.; Ji, P.; Fang, Z.; Liu, F.; Liu, Y.; Pan, Y.; dos-Santos-Silva, I.; He, Z.; Ke, Y. Estimating cancer incidence based on claims data from medical insurance systems in two areas lacking cancer registries in China. EClinicalMedicine, 2020, 20100312
[http://dx.doi.org/10.1016/j.eclinm.2020.100312] [PMID: 32215367]
[4]
Coit, D.G.; Andtbacka, R.; Anker, C.J.; Bichakjian, C.K.; Carson, W.E., III; Daud, A.; DiMaio, D.; Fleming, M.D.; Guild, V.; Halpern, A.C.; Hodi, F.S., Jr; Kelley, M.C.; Khushalani, N.I.; Kudchadkar, R.R.; Lange, J.R.; Lind, A.; Martini, M.C.; Olszanski, A.J.; Pruitt, S.K.; Ross, M.I.; Swetter, S.M.; Tanabe, K.K.; Thompson, J.A.; Trisal, V.; Urist, M.M.; McMillian, N.; Ho, M. Melanoma, Version 2.2013. J. Natl. Compr. Canc. Netw., 2013, 11(4), 395-407.
[http://dx.doi.org/10.6004/jnccn.2013.0055] [PMID: 23584343]
[5]
Liu, Q.; Zeng, X.; Wang, W.; Huang, R.; Huang, Y.; Liu, S.; Huang, Y.; Wang, Y.; Fang, Q.; He, G.; Zeng, Y. Awareness of risk factors and warning symptoms and attitude towards gastric cancer screening among the general public in China: A cross-sectional study. BMJ Open, 2019, 9(7)e029638
[http://dx.doi.org/10.1136/bmjopen-2019-029638] [PMID: 31340970]
[6]
Tan, P.; Yeoh, K-G. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology, 2015, 149(5), 1153-1162.
[http://dx.doi.org/10.1053/j.gastro.2015.05.059]
[7]
Smyth, E.C.; Nilsson, M.; Grabsch, H.I.; van Grieken, N.C.T.; Lordick, F. Gastric cancer. Lancet, 2020, 396(10251), 635-648.
[http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]
[8]
De Re, V. Molecular features distinguish gastric cancer subtypes. Int. J. Mol. Sci., 2018, 19(10), 3121.
[http://dx.doi.org/10.3390/ijms19103121] [PMID: 30314372]
[9]
Patel, T.H.; Cecchini, M. Targeted therapies in advanced gastric cancer. Curr. Treat. Options Oncol., 2020, 21(9), 70.
[http://dx.doi.org/10.1007/s11864-020-00774-4] [PMID: 32725377]
[10]
Zhang, P.; Chao, Z.; Zhang, R.; Ding, R.; Wang, Y.; Wu, W.; Han, Q.; Li, C.; Xu, H.; Wang, L.; Xu, Y. Circular RNA regulation of myogenesis. Cells, 2019, 8(8), 885.
[http://dx.doi.org/10.3390/cells8080885] [PMID: 31412632]
[11]
Wang, K.; Long, B.; Liu, F.; Wang, J.X.; Liu, C.Y.; Zhao, B.; Zhou, L.Y.; Sun, T.; Wang, M.; Yu, T.; Gong, Y.; Liu, J.; Dong, Y.H.; Li, N.; Li, P.F. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur. Heart J., 2016, 37(33), 2602-2611.
[http://dx.doi.org/10.1093/eurheartj/ehv713] [PMID: 26802132]
[12]
Lukiw, W.J. Circular RNA (circRNA) in Alzheimer’s disease (AD). Front. Genet., 2013, 4, 307.
[http://dx.doi.org/10.3389/fgene.2013.00307] [PMID: 24427167]
[13]
Guarnerio, J.; Bezzi, M.; Jeong, J.C.; Paffenholz, S.V.; Berry, K.; Naldini, M.M.; Lo-Coco, F.; Tay, Y.; Beck, A.H.; Pandolfi, P.P. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell, 2016, 165(2), 289-302.
[http://dx.doi.org/10.1016/j.cell.2016.03.020] [PMID: 27040497]
[14]
Yang, H.; Zhang, H.; Yang, Y.; Wang, X.; Deng, T.; Liu, R.; Ning, T.; Bai, M.; Li, H.; Zhu, K.; Li, J.; Fan, Q.; Ying, G.; Ba, Y. Hypoxia induced exosomal circRNA promotes metastasis of colorectal cancer via targeting GEF-H1/RhoA axis. Theranostics, 2020, 10(18), 8211-8226.
[http://dx.doi.org/10.7150/thno.44419] [PMID: 32724467]
[15]
Han, T.S.; Hur, K.; Cho, H.S.; Ban, H.S. Epigenetic associations between lncRNA/circRNA and miRNA in hepatocellular carcinoma. Cancers (Basel), 2020, 12(9), 2622.
[http://dx.doi.org/10.3390/cancers12092622] [PMID: 32937886]
[16]
Liang, G.; Ling, Y.; Mehrpour, M.; Saw, P.E.; Liu, Z.; Tan, W.; Tian, Z.; Zhong, W.; Lin, W.; Luo, Q.; Lin, Q.; Li, Q.; Zhou, Y.; Hamai, A.; Codogno, P.; Li, J.; Song, E.; Gong, C. Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression. Mol. Cancer, 2020, 19(1), 65.
[http://dx.doi.org/10.1186/s12943-020-01152-2] [PMID: 32213200]
[17]
Wilusz, J.E.; Sharp, P.A. Molecular biology. A circuitous route to noncoding RNA. Science, 2013, 340(6131), 440-441.
[http://dx.doi.org/10.1126/science.1238522] [PMID: 23620042]
[18]
Meng, S.; Zhou, H.; Feng, Z.; Xu, Z.; Tang, Y.; Li, P.; Wu, M. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol. Cancer, 2017, 16(1), 94.
[http://dx.doi.org/10.1186/s12943-017-0663-2] [PMID: 28535767]
[19]
Pan, H.; Li, T.; Jiang, Y.; Pan, C.; Ding, Y.; Huang, Z.; Yu, H.; Kong, D. Overexpression of circular RNA ciRS‐7 abrogates the tumor suppressive effect of miR‐7 on gastric cancer via PTEN/PI3K/AKT signaling pathway. J. Cell. Biochem., 2018, 119(1), 440-446.
[http://dx.doi.org/10.1002/jcb.26201] [PMID: 28608528]
[20]
Li, P.; Chen, H.; Chen, S.; Mo, X.; Li, T.; Xiao, B.; Yu, R.; Guo, J. Circular RNA 0000096 affects cell growth and migration in gastric cancer. Br. J. Cancer, 2017, 116(5), 626-633.
[http://dx.doi.org/10.1038/bjc.2016.451] [PMID: 28081541]
[21]
Lai, Z.; Yang, Y.; Yan, Y.; Li, T.; Li, Y.; Wang, Z.; Shen, Z.; Ye, Y.; Jiang, K.; Wang, S. Analysis of co-expression networks for circular RNAs and mRNAs reveals that circular RNAs hsa_circ_0047905, hsa_circ_0138960 and has-circRNA7690-15 are candidate oncogenes in gastric cancer. Cell Cycle, 2017, 16(23), 2301-2311.
[http://dx.doi.org/10.1080/15384101.2017.1380135] [PMID: 28980874]
[22]
Hu, J.; Qiu, D.; Yu, A.; Hu, J.; Deng, H.; Li, H.; Yi, Z.; Chen, J.; Zu, X. YTHDF1 is a potential pan-cancer biomarker for prognosis and immunotherapy. Front. Oncol., 2021, 11607224
[http://dx.doi.org/10.3389/fonc.2021.607224] [PMID: 34026603]
[23]
Lánczky, A. Győrffy, B. Web-based survival analysis tool tailored for medical research (KMplot): Development and implementation. J. Med. Internet Res., 2021, 23(7)e27633
[http://dx.doi.org/10.2196/27633] [PMID: 34309564]
[24]
Tang, Z.; Kang, B.; Li, C.; Chen, T.; Zhang, Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res., 2019, 47(W1), W556-W560.
[http://dx.doi.org/10.1093/nar/gkz430] [PMID: 31114875]
[25]
Barbaric, D.; Dalla-Pozza, L.; Byrne, J.A. A reliable method for total RNA extraction from frozen human bone marrow samples taken at diagnosis of acute leukaemia. J. Clin. Pathol., 2002, 55(11), 865-867.
[http://dx.doi.org/10.1136/jcp.55.11.865] [PMID: 12401828]
[26]
Bustin, S.A. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): Trends and problems. J. Mol. Endocrinol., 2002, 29(1), 23-39.
[http://dx.doi.org/10.1677/jme.0.0290023] [PMID: 12200227]
[27]
Ang, T.L.; Fock, K.M. Clinical epidemiology of gastric cancer. Singapore Med. J., 2014, 55(12), 621-628.
[http://dx.doi.org/10.11622/smedj.2014174] [PMID: 25630323]
[28]
Zhao, Y.; Zheng, R.; Chen, J.; Ning, D. CircRNA CDR1as/miR-641/HOXA9 pathway regulated stemness contributes to cisplatin resistance in non-small cell lung cancer (NSCLC). Cancer Cell Int., 2020, 20(1), 289.
[http://dx.doi.org/10.1186/s12935-020-01390-w] [PMID: 32655321]
[29]
Li, P.; Yang, X.; Yuan, W.; Yang, C.; Zhang, X.; Han, J.; Wang, J.; Deng, X.; Yang, H.; Li, P.; Tao, J.; Lu, Q.; Gu, M. CircRNA-Cdr1as exerts anti-oncogenic functions in bladder Cancer by sponging MicroRNA-135a. Cell. Physiol. Biochem., 2018, 46(4), 1606-1616.
[http://dx.doi.org/10.1159/000489208] [PMID: 29694981]
[30]
Su, Y.; Lv, X.; Yin, W.; Zhou, L.; Hu, Y.; Zhou, A.; Qi, F. CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression. Aging, 2019, 11(19), 8183-8203.
[http://dx.doi.org/10.18632/aging.102312] [PMID: 31581132]
[31]
Li, P.; Xue, W.J.; Feng, Y.; Mao, Q.S. Long non-coding RNA CASC2 suppresses the proliferation of gastric cancer cells by regulating the MAPK signaling pathway. Am. J. Transl. Res., 2016, 8(8), 3522-3529.
[PMID: 27648142]
[32]
Zeng, Z.; Luo, F.; Zou, L.; He, R.; Pan, D.; Chen, X.; Xie, T.; Li, Y.; Peng, Z.; Chen, G. Human papillomavirus as a potential risk factor for gastric cancer: A meta-analysis of 1,917 cases. OncoTargets Ther., 2016, 9, 7105-7114.
[http://dx.doi.org/10.2147/OTT.S115053] [PMID: 27895502]
[33]
Wang, K.; Liu, R.; Li, J.; Mao, J.; Lei, Y.; Wu, J.; Zeng, J.; Zhang, T.; Wu, H.; Chen, L.; Huang, C.; Wei, Y. Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling. Autophagy, 2011, 7(9), 966-978.
[http://dx.doi.org/10.4161/auto.7.9.15863] [PMID: 21610320]
[34]
Heckmann, B.L.; Zhang, X.; Xie, X.; Liu, J. The G0/G1 switch gene 2 (G0S2): Regulating metabolism and beyond. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2013, 1831(2), 276-281.
[http://dx.doi.org/10.1016/j.bbalip.2012.09.016]
[35]
Choi, H.; Lee, H.; Kim, T-H.; Kim, H.J.; Lee, Y.J.; Lee, S.J.; Yu, J.H.; Kim, D.; Kim, K-S.; Park, S.W.; Kim, J. G0/G1 switch gene 2 has a critical role in adipocyte differentiation. Cell Death Differ., 2014, 21(7), 1071-1080.
[http://dx.doi.org/10.1038/cdd.2014.26] [PMID: 24583640]
[36]
Yim, C.Y.; Bikorimana, E.; Khan, E.; Warzecha, J.M.; Shin, L.; Rodriguez, J.; Dmitrovsky, E.; Freemantle, S.J.; Spinella, M.J. G0S2 represses PI3K/mTOR signaling and increases sensitivity to PI3K/mTOR pathway inhibitors in breast cancer. Cell Cycle, 2017, 16(21), 2146-2155.
[http://dx.doi.org/10.1080/15384101.2017.1371884] [PMID: 28910567]
[37]
Yim, C.Y. G0S2 functions as a tumor suppressor gene through inhibition of c-Myc; AACR, 2015.
[38]
Wedeken, L.; Ohnheiser, J.; Hirschi, B.; Wethkamp, N.; Klempnauer, K.H. Association of tumor suppressor protein Pdcd4 with ribosomes is mediated by protein-protein and protein-RNA interactions. Genes Cancer, 2010, 1(3), 293-301.
[http://dx.doi.org/10.1177/1947601910364227] [PMID: 21779451]
[39]
Chen, Y. Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. J. Pathol., 2003, 200(5), 640-646.
[http://dx.doi.org/10.1002/path.1378]
[40]
Afonja, O.; Juste, D.; Das, S.; Matsuhashi, S.; Samuels, H.H. Induction of PDCD4 tumor suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis. Oncogene, 2004, 23(49), 8135-8145.
[http://dx.doi.org/10.1038/sj.onc.1207983] [PMID: 15361828]
[41]
Mudduluru, G.; Medved, F.; Grobholz, R.; Jost, C.; Gruber, A.; Leupold, J.H.; Post, S.; Jansen, A.; Colburn, N.H.; Allgayer, H. Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer, 2007, 110(8), 1697-1707.
[http://dx.doi.org/10.1002/cncr.22983] [PMID: 17849461]
[42]
Zhang, H.; Ozaki, I.; Mizuta, T.; Hamajima, H.; Yasutake, T.; Eguchi, Y.; Ideguchi, H.; Yamamoto, K.; Matsuhashi, S. Involvement of programmed cell death 4 in transforming growth factor-β1-induced apoptosis in human hepatocellular carcinoma. Oncogene, 2006, 25(45), 6101-6112.
[http://dx.doi.org/10.1038/sj.onc.1209634] [PMID: 16682950]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy