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LncRNA CASC9 Suppressed the Apoptosis of Gastric Cancer Cells through Regulating BMI1

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Pathology & Oncology Research

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Abstract

Long noncoding RNAs (lncRNAs) play important roles in regulating the apoptosis of gastric cancer (GC) cells. This study aims to investigate the underlying mechanism of lncRNA CASC9 in regulating the apoptosis of GC cells. The expressions of lncRNA and protein in GC tissues and cell lines were detected by qRT-PCR and western blot. GC cell apoptosis was detected by flow cytometry analysis. RNA pull-down and RNA immunoprecipitation (RIP) assays were conducted to verify the interaction between CASC9 and BMI1. LncRNA CASC9 was upregulated in GC tissue and GC cells, and high CASC9 expression was positively correlated with TNM stage and lymph node metastasis. Silencing CASC9 promoted the apoptosis of GC cells. LncRNA CASC9 could interact with BMI1 and positively regulate BMI1 expression. Silencing CASC9 promoted the ubiquitination of BMI1. In addition, lncRNA CASC9 regulated the apoptosis of GC cells through BMI1. Furthermore, interfering CASC9 inhibited the tumor growth of GC. LncRNA CASC9 could interact with BMI1 to regulate the degradation of BMI1, thus to affect the apoptosis of GC cells and suppressed tumor growth.

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References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30

    Article  Google Scholar 

  2. Ge S et al (2012) Association between habitual dietary salt intake and risk of gastric Cancer: a systematic review of observational studies. Gastroenterol Res Pract 2012:808120–808120

    Article  Google Scholar 

  3. Seo AN et al (2019) Exon 9 mutation of PIK3CA associated with poor survival in patients with Epstein-Barr virus-associated gastric Cancer. Anticancer Res 39(4):2145–2154

    Article  Google Scholar 

  4. Aoyama T, Yoshikawa T (2017) Adjuvant therapy for locally advanced gastric cancer. Surg Today 47(11):1295–1302

    Article  Google Scholar 

  5. Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, Marcos-Gragera R, Stiller C, Azevedo e Silva G, Chen WQ, Ogunbiyi OJ, Rachet B, Soeberg MJ, You H, Matsuda T, Bielska-Lasota M, Storm H, Tucker TC, Coleman MP (2015) Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet (London, England) 385(9972):977–1010

    Article  Google Scholar 

  6. Wang MW, Liu J, Liu Q, Xu QH, Li TF, Jin S, Xia TS (2017) LncRNA SNHG7 promotes the proliferation and inhibits apoptosis of gastric cancer cells by repressing the P15 and P16 expression. Eur Rev Med Pharmacol Sci 21(20):4613–4622

    PubMed  Google Scholar 

  7. Li P, Zhou X, Sun W, Sheng W, Tu Y, Yu Y, Dong J, Ye B, Zheng Z, Lu M (2017) Elemene induces apoptosis of human gastric Cancer cell line BGC-823 via extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. Med Sci Monitor 23:809–817

    Article  CAS  Google Scholar 

  8. Zhang S, Zhang X, Sun Q, Zhuang C, Li G, Sun L, Wang H (2019) LncRNA NR2F2-AS1 promotes tumourigenesis through modulating BMI1 expression by targeting miR-320b in non-small cell lung cancer. J Cell Mol Med 23(3):2001–2011

    Article  CAS  Google Scholar 

  9. Zhao T, Chen Y, Sheng S, Wu Y, Zhang T (2018) Upregulating microRNA-498 inhibits gastric cancer proliferation invasion and chemoresistance through inverse interaction of Bmi1. Cancer Gene Ther

  10. Chen Y, Lian G, Zhang Q, Zeng L, Qian C, Chen S, Huang K (2013) Overexpression of Bmi-1 induces the malignant transformation of gastric epithelial cells in vitro. Oncol Res 21(1):33–41

    Article  CAS  Google Scholar 

  11. Gao F-L, Li WS, Liu CL, Zhao GQ (2013) Silencing Bmi-1 enhances the senescence and decreases the metastasis of human gastric cancer cells. World J Gastroenterol 19(46):8764–8769

    Article  CAS  Google Scholar 

  12. Liu P, Zhang M, Niu Q, Zhang F, Yang Y, Jiang X (2018) Knockdown of long non-coding RNA ANRIL inhibits tumorigenesis in human gastric cancer cells via microRNA-99a-mediated down-regulation of BMI1. Braz J Med Biol Res 51(10):e6839–e6839

    Article  Google Scholar 

  13. Sahasrabuddhe AA, Dimri M, Bommi PV, Dimri GP (2011) βTrCP regulates BMI1 protein turnover via ubiquitination and degradation. Cell cycle (Georgetown, Tex) 10(8):1322–1330

    Article  CAS  Google Scholar 

  14. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166

    Article  CAS  Google Scholar 

  15. Peng WX, Koirala P, Mo YY (2017) LncRNA-mediated regulation of cell signaling in cancer. Oncogene 36(41):5661–5667

    Article  CAS  Google Scholar 

  16. Zhang E, He X, Zhang C, Su J, Lu X, Si X, Chen J, Yin D, Han L, de W (2018) A novel long noncoding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by binding to YBX1. Genome Biol 19(1):154–154

    Article  Google Scholar 

  17. Xue M, Chen LY, Wang WJ, Su TT, Shi LH, Wang L, Zhang W, Si JM, Wang LJ, Chen SJ (2018) HOTAIR induces the ubiquitination of Runx3 by interacting with Mex3b and enhances the invasion of gastric cancer cells. Gastric Cancer 21(5):756–764

    Article  CAS  Google Scholar 

  18. Klingenberg M, Groß M, Goyal A, Polycarpou-Schwarz M, Miersch T, Ernst AS, Leupold J, Patil N, Warnken U, Allgayer H, Longerich T, Schirmacher P, Boutros M, Diederichs S (2018) The long noncoding RNA Cancer susceptibility 9 and RNA binding protein heterogeneous nuclear ribonucleoprotein L form a complex and Coregulate genes linked to AKT signaling. Hepatology 68(5):1817–1832

    Article  CAS  Google Scholar 

  19. Jiang F, Qi W, Wang Y, Wang W, Fan L (2019) lncRNA PEG10 promotes cell survival, invasion and migration by sponging miR-134 in human bladder cancer. Biomed Pharmacother 114:108814

    Article  CAS  Google Scholar 

  20. Zhai W et al (2019) A positive feed-forward loop between LncRNA-URRCC and EGFL7/P-AKT/FOXO3 signaling promotes proliferation and metastasis of clear cell renal cell carcinoma. Mol Cancer 18(1):81

    Article  Google Scholar 

  21. Shao G et al (2019) lncRNA CASC9 positively regulates CHK1 to promote breast cancer cell proliferation and survival through sponging the miR-195/497 cluster. Int J Oncol 54(5):1665–1675

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Yang Y, Chen D, Liu H, Yang K (2019) Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma. Cell Death Dis 10(2):41–41

    Article  Google Scholar 

  23. Li X, Chen B, Chi D, Zhang Y, Jiang W (2019) lncRNA CASC9 regulates cell migration and invasion in hemangioma endothelial cells by targeting miR-125a-3p/Nrg1. OncoTargets Ther 12:423–432

    Article  CAS  Google Scholar 

  24. Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914

    Article  CAS  Google Scholar 

  25. Liu Z, Chen Z, Fan R, Jiang B, Chen X, Chen Q, Nie F, Lu K, Sun M (2017) Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer. Mol Cancer 16(1):82–82

    Article  Google Scholar 

  26. Li W, Yu X, Xia Z, Yu X, Xie L, Ma X, Zhou H, Liu L, Wang J, Yang Y, Liu H (2018) Repression of Noxa by Bmi1 contributes to deguelin-induced apoptosis in non-small cell lung cancer cells. J Cell Mol Med 22(12):6213–6227

    Article  CAS  Google Scholar 

  27. Kim M, Lee S, Park WH, Suh DH, Kim K, Kim YB, No JH (2018) Silencing Bmi1 expression suppresses cancer stemness and enhances chemosensitivity in endometrial cancer cells. Biomed Pharmacother 108:584–589

    Article  CAS  Google Scholar 

  28. Wang Y, Lv H, Xu Z, Sun J, Ni Y, Chen Z, Cheng X (2019) Huaier n-butanol extract suppresses proliferation and metastasis of gastric cancer via c-Myc-Bmi1 axis. Sci Rep 9(1):447–447

    Article  Google Scholar 

  29. Zhang X-W, Sheng YP, Li Q, Qin W, Lu YW, Cheng YF, Liu BY, Zhang FC, Li J, Dimri GP, Guo WJ (2010) BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer. Mol Cancer 9:40–40

    Article  CAS  Google Scholar 

  30. Li W, Li Y, Tan Y, Ma K, Cui J (2010) Bmi-1 is critical for the proliferation and invasiveness of gastric carcinoma cells. J Gastroenterol Hepatol 25(3):568–575

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Rd., Hefei, 230022, Anhui, People’s Republic of China

    Jun Fang, Wei Chen & Xiang-Ling Meng

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  1. Jun Fang
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  2. Wei Chen
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  3. Xiang-Ling Meng
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Correspondence to Jun Fang.

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Fang, J., Chen, W. & Meng, XL. LncRNA CASC9 Suppressed the Apoptosis of Gastric Cancer Cells through Regulating BMI1. Pathol. Oncol. Res. 26, 475–482 (2020). https://doi.org/10.1007/s12253-019-00703-3

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  • DOI: https://doi.org/10.1007/s12253-019-00703-3

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