Fusobacterium nucleatum promotes the development of colorectal carcinoma by targeting lncRNA NEAT1

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Journal of Microbes and Infections ›› 2022, Vol. 17 ›› Issue (5) : 282-289.

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Abstract

The aim of this study was to investigate the effects of Fusobacterium nucleatum (F. nucleatum) on proliferation and apoptosis of human colorectal cancer (CRC) cells as well as its mechanism. Human CRC cells HCT116 at logarithmic growth stage were divided into control group, F. nucleatum group (infected with F. nucleatum), si-NEAT1 group (transfected with si-NEAT1) and F. nucleatum+si-NEAT1 group (infected with F. nucleatum after transfection with si-NEAT1). qRT-PCR was used to measure the level of RNA in cells. CCK-8 assay was performed to detect the proliferation of cells, while flow cytometry was used to calculate the apoptosis rate of cells. The expression levels of apoptosis related proteins caspase-3, Bcl-2 and Bax were determined by western blot. The proliferation of cells was enhanced, and the apoptosis rate of cells was downregulated. The expressions of caspase-3 and Bax were decreased, while the level of Bcl-2 was lifted. In addition, the expression of NEAT1 in CRC cells increased after infection with F. nucleatum. After transfection with si-NEAT1, the proliferation ability of CRC cells was decreased, the apoptosis rate was increased, and the expressions of caspase-3 and Bax protein were added, while the expression of Bcl-2 was reduced. Knockdown NEAT1 expression reversed the effect of F. nucleatum on proliferation and apoptosis of CRC cells. These results suggested that F. nucleatum could promote the proliferation and inhibit the apoptosis of CRC cells by up-regulating of NEAT1.

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Fusobacterium nucleatum promotes the development of colorectal carcinoma by targeting lncRNA NEAT1[J]. Journal of Microbes and Infections. 2022, 17(5): 282-289

References

[1]Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al.Colorectal cancer statistics, 2020[J].CA Cancer J Clin., 2020, 70(3):145-164
[2]Zhu Y, Wang C, Becker SA, Hurst K, Nogueira LM, Findlay VJ, et al.miR-145 Antagonizes SNAI1-Mediated Stemness and Radiation Resistance in Colorectal Cancer[J].Mol Ther, 2018, 26(3):744-754
[3]Ma YS, Li W, Liu Y, Shi Y, Lin QL, Fu D.Targeting Colorectal Cancer Stem Cells as an Effective Treatment for Colorectal Cancer[J].Technol Cancer Res Treat, 2020, 19:1533033819892261-1533033819892261
[4]Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Relman DA.The application of ecological theory toward an understanding of the human microbiome[J].Science, 2012, 336(6086):1255-1262
[5]Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, et al.Fusobacterium in colonic flora and molecular features of colorectal carcinoma[J].Cancer Res, 2014, 74(5):1311-1318
[6]Belcheva A, Irrazabal T, Robertson SJ, Streutker C, Maughan H, Rubino S, et al.Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells[J].Cell, 2014, 158(2):288-299
[7]Brennan CA, Garrett WS.Fusobacterium nucleatum - symbiont, opportunist and oncobacterium[J].Nat Rev Microbiol, 2019, 17(3):156-166
[8]Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et al.Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment[J].Cell Host Microbe, 2013, 14(2):207-215
[9]Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, et al.Genomic analysis identifies association of Fusobacterium with colorectal carcinoma[J].Genome Res, 2012, 22(2):292-298
[10]Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, et al.Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis[J].Gut, 2016, 65(12):1973-1980
[11]Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, et al.Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy[J].Cell, 2017, 170(3):548-563
[12]Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H, et al.Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer[J].World J Gastroenterol, 2016, 22(2):557-566
[13]Parhi L, Alon-Maimon T, Sol A, Nejman D, Shhadeh A, Fainsod-Levi T, et al.Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression[J].Nat Commun, 2020, 11(1):3259-3259
[14]Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al.Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma[J].Genome Res, 2012, 22(2):299-306
[15]Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, et al.Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer[J].Science, 2017, 358(6369):1443-1448
[16]Lv Y, Yang X, Wang L.Effect of lncRNA THOR on proliferation and migration of colon cancer cells[J].Oncol Lett, 2019, 18(3):2518-2522
[17]Cheng B, Rong A, Zhou Q, Li W.LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway[J].J Exp Clin Cancer Res, 2020, 39(1):5-5
[18]Xia TF, Chen J, Wu K, Zhang J, Yan Q.Long noncoding RNA NEAT1 promotes the growth of gastric cancer cells by regulating miR-497-5p/PIK3R1 axis[J].Eur Rev Med Pharmacol Sci, 2019, 23(16):6914-6926
[19]Wang J, Su Z, Lu S, Fu W, Liu Z, Jiang X, et al.LncRNA HOXA-AS2 and its molecular mechanisms in human cance[J].Clin Chim Acta, 2018, 485:229-233
[20]Yue B, Liu C, Sun H, Liu M, Song C, Cui R, et al.A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/beta-Catenin Signaling Promotes Metastasis of Colon Cancer[J].Mol Ther, 2018, 26(5):1287-1298
[21]Peng CL, Zhao XJ, Wei CC, Wu JW.LncRNA HOTAIR promotes colon cancer development by down-regulating miRNA-34a[J].Eur Rev Med Pharmacol Sci, 2019,, 23(13):5752-5761
[22]He Z, Dang J, Song A, Cui X, Ma Z, Zhang Z.NEAT1 promotes colon cancer progression through sponging miR-495-3p and activating CDK6 in vitro and in vivo[J].J Cell Physiol, 2019, 234(11):19582-19591