Post-transcriptional Gene Regulation in Colitis Associated Cancer

Overview

Journal Front Genet

Date 2019 Jul 6

PMID 31275360

Citations 9

Authors

Gang Chen

Yuan Feng

Xuezheng Li

Zhe Jiang

Bei Bei

Lin Zhang

Yueqing Han

Yanwu Li

Ning Li

Affiliations

Soon will be listed here.

Abstract

Colitis-associated cancer (CAC) has been linked to microRNA (miRNA) aberrant expression elicited by inflammation. In this study, we used the AOM/DSS-induced CAC mice model to explore the ectopic expression of miRNAs in the precancerous stage of CAC. As a result, we found that miR-31-5p, miR-223-3p, and let-7f-5p were dysregulated during the development of intestinal dysplasia. Subsequently, we first identified the role of these three miRNAs in CAC. Adenomatous polyposis coli (APC) was revealed as a new target of miR-223-3p, and solute carrier family 9- subfamily A-member 9 (SLC9A9) and APC membrane recruitment protein 3 (AMER3) were suggested as two new targets for let-7f-5p. For miR-31-5p, we proved that it can target LATS2 mRNA so as to modulate Hippo pathway in Caco2 cells. Second, to examine if targeting these three miRNAs would lead to CAC prevention, pedunculoside, a natural triterpene glycoside capable of rescuing the down-regulation of LATS2 and APC caused by either miR-31-5p or miR-223-3p overexpression, respectively, was used in the AOM/DSS-induced CAC model. The results showed that pedunculoside (25 mg/kg) substantially mitigated the damage to mice intestine caused by DSS/AOM. These results suggested that miRNAs-elicited post-transcriptional regulation is involved in the pathogenesis of CAC, and CAC can be prevented through targeting key miRNAs that are ectopically expressed in CAC.

Citing Articles

Chronic Gastrointestinal Disorders and miRNA-Associated Disease: An Up-to-Date.

Giammona A, Galuzzi B, Imperia E, Gervasoni C, Remedia S, Restaneo L Int J Mol Sci. 2025; 26(1.

PMID: 39796266 PMC: 11720538. DOI: 10.3390/ijms26010413.

Endosomal pH is an evolutionarily conserved driver of phenotypic plasticity in colorectal cancer.

Prasad H, Bv H, Subbalakshmi A, Mandal S, Jolly M, Visweswariah S NPJ Syst Biol Appl. 2024; 10(1):149.

PMID: 39702657 PMC: 11659597. DOI: 10.1038/s41540-024-00463-0.

The MicroRNA miR-223 Constrains Colitis-associated Tumorigenesis by Limiting Myeloid Cell Infiltration and Chemokine Expression.

Flynn C, Markey G, Neudecker V, Farrelly C, Furuta G, Eltzschig H J Immunol. 2024; 213(12):1869-1883.

PMID: 39485006 PMC: 11611642. DOI: 10.4049/jimmunol.2400129.

Preclinical metabolism and metabolic drug-drug interaction profile of pedunculoside and rotundic acid.

Wu L, Dong L, Zhou Z, Wang X, Lin Y, Shi X Clin Transl Sci. 2024; 17(10):e70043.

PMID: 39392387 PMC: 11469747. DOI: 10.1111/cts.70043.

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer.

Jones A, Scheurlen K, MacLeod A, Simon H, Galandiuk S Cancers (Basel). 2024; 16(7).

PMID: 38611081 PMC: 11010915. DOI: 10.3390/cancers16071403.

References

Eaden J, Abrams K, Mayberry J . The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001; 48(4):526-35. PMC: 1728259. DOI: 10.1136/gut.48.4.526. View

Canavan C, Abrams K, Mayberry J . Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease. Aliment Pharmacol Ther. 2006; 23(8):1097-104. DOI: 10.1111/j.1365-2036.2006.02854.x. View

Rubin D, Shaker A, Levin M . Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer. Front Immunol. 2012; 3:107. PMC: 3347037. DOI: 10.3389/fimmu.2012.00107. View

Brauburger K, Akyildiz S, Ruppert J, Graeb M, Bernkopf D, Hadjihannas M . Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt-β-catenin signalling. FEBS J. 2013; 281(3):787-801. DOI: 10.1111/febs.12624. View

Kim H, Kwon H, Ha Thi H, Lee H, Kim G, Hahm K . MicroRNA-132 and microRNA-223 control positive feedback circuit by regulating FOXO3a in inflammatory bowel disease. J Gastroenterol Hepatol. 2016; 31(10):1727-1735. DOI: 10.1111/jgh.13321. View

Wang H, Chao K, Ng S, Bai A, Yu Q, Yu J . Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease. Genome Biol. 2016; 17:58. PMC: 4815271. DOI: 10.1186/s13059-016-0901-8. View

Hong A, Meng Z, Guan K . The Hippo pathway in intestinal regeneration and disease. Nat Rev Gastroenterol Hepatol. 2016; 13(6):324-37. PMC: 5642988. DOI: 10.1038/nrgastro.2016.59. View

Kim H, Kim M, Park Y, Park I, Kim T, Yang S . Prostaglandin E Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice. Gastroenterology. 2016; 152(3):616-630. PMC: 5285392. DOI: 10.1053/j.gastro.2016.11.005. View

Li M, Zhang S, Qiu Y, He Y, Chen B, Mao R . Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3. Cell Death Dis. 2017; 8(3):e2699. PMC: 5386569. DOI: 10.1038/cddis.2017.76. View

10.

Luan L, Shi J, Yu Z, Andl T . The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation. Exp Dermatol. 2017; 26(6):497-504. DOI: 10.1111/exd.13355. View

11.

Zhang L, Shay J . Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer. J Natl Cancer Inst. 2017; 109(8). PMC: 5963831. DOI: 10.1093/jnci/djw332. View

12.

Ueda M, Iguchi T, Masuda T, Komatsu H, Nambara S, Sakimura S . Up-regulation of Promotes Cancer Progression and Is Involved in Poor Prognosis in Colorectal Cancer. Anticancer Res. 2017; 37(5):2255-2263. DOI: 10.21873/anticanres.11562. View

13.

Tian Y, Ma X, Lv C, Sheng X, Li X, Zhao R . Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis. Elife. 2017; 6. PMC: 5584991. DOI: 10.7554/eLife.29538. View

14.

Gao Y, Yi J, Zhang K, Bai F, Feng B, Wang R . Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2017; 36(1):161. PMC: 5689139. DOI: 10.1186/s13046-017-0622-1. View

15.

Soroosh A, Koutsioumpa M, Pothoulakis C, Iliopoulos D . Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2017; 314(2):G256-G262. PMC: 5866423. DOI: 10.1152/ajpgi.00268.2017. View

16.

Jacob H, Stanisavljevic L, Eeg Storli K, Hestetun K, Dahl O, Myklebust M . Identification of a sixteen-microRNA signature as prognostic biomarker for stage II and III colon cancer. Oncotarget. 2017; 8(50):87837-87847. PMC: 5675676. DOI: 10.18632/oncotarget.21237. View

17.

Tili E, Michaille J, Piurowski V, Rigot B, Croce C . MicroRNAs in intestinal barrier function, inflammatory bowel disease and related cancers-their effects and therapeutic potentials. Curr Opin Pharmacol. 2017; 37:142-150. PMC: 5938753. DOI: 10.1016/j.coph.2017.10.010. View

18.

Guo Y, Xiong J, Wang J, Wen J, Zhi F . Inhibition of Rac family protein impairs colitis and colitis-associated cancer in mice. Am J Cancer Res. 2018; 8(1):70-80. PMC: 5794722. View

19.

Gwiggner M, Martinez-Nunez R, Whiteoak S, Bondanese V, Claridge A, Collins J . MicroRNA-31 and MicroRNA-155 Are Overexpressed in Ulcerative Colitis and Regulate IL-13 Signaling by Targeting Interleukin 13 Receptor α-1. Genes (Basel). 2018; 9(2). PMC: 5852581. DOI: 10.3390/genes9020085. View

20.

Chung K, Cheon S, Roh S, Lee M, An H . Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice. Nutrients. 2018; 10(2). PMC: 5852778. DOI: 10.3390/nu10020202. View