Investigation of significant microRNA-mRNA pairs associated with nonspecific digestive disorder in rabbits

X. Jia, Q. Liao, S. Chen, J. Wang, S. Lai


Nonspecific digestive disorders (NSDD) are one of the major intestinal problems in rabbit, with considerable economic losses in industrial rabbit farms. MicroRNAs (miRNAs), as small non-coding RNAs, have significant biological involvement in intestinal disorders. In this study, we investigated the expression levels of 25 genes and 25 miRNAs in ileum, rabbit sacculus rotundus (RSR) and colon tissues from 9 rabbits with different severity of NSDD. These molecules have been found to be related to NSDD or inflammatory bowel disease, which will help recognise the miRNA-mRNA pairs. Finally, 108 possible pairs of miRNA-mRNA pairs with an anti-correlation were identified by Pearson’s correlation analysis between differentially expressed 25 miRNAs and 23 mRNAs. Ninety-five of these miRNA-mRNA pairs were hitherto unexplored, and their roles in NSDD biology require further elucidation. Our results give a clue to the potential miRNA-mRNA pairs for the NSDD that can further improve the understanding of the pathogenesis of NSDD in rabbit.


nonspecific digestive disorders; rabbit; miRNAs; gene regulation; anti-correlation

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Bartel D.P. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116: 281-297.

Bennegadi N., Gidenne T., Licois D. 2001. Impact of fibre deficiency and sanitary statuson non-specific enteropathy of the growing rabbit. Anim. Res., 50: 401-413.

Carethers J.M., Braun J., Sands B.E. 2015. Genetics, Genetic Testing, and Biomarkers of Digestive Diseases. Gastroenterology, 149: 1131-1133.

Chen S.Y., Zhang W.X., Zhang G.W., Peng J., Zhao X.B., Lai S.J. 2013a. Case-control study and mRNA expression analysis reveal the MyD88 gene is associated with digestive disorders in rabbit. Anim. Genet., 44: 703-710.

Chen Y., Xiao Y., Ge W., Zhou K., Wen J., Yan W., Wang Y., Wang B., Qu C., Wu J., Xu L., Cai W. 2013b. miR-200b inhibits TGF-beta1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells. Cell Death Dis., 4: e541.

D’Angelo B., Benedetti E., Cimini A., Giordano A. 2016. MicroRNAs: A Puzzling Tool in Cancer Diagnostics and Therapy. Anticancer Res., 36: 5571-5575.

DeCubellis J., Graham J. 2013. Gastrointestinal disease in guinea pigs and rabbits. The veterinary clinics of North America. Vet. Clin. Exot. Anim., 16: 421-435.

Feng X., Wang H., Ye S.C., Guan J.X., Tan W.K., Cheng S., Wei G.L., Wu W.Y., Wu F., Zhou Y. 2012. Up-Regulation of microRNA-126 May Contribute to Pathogenesis of Ulcerative Colitis via Regulating NF-kappaB Inhibitor IκBα. PloS One, 7.

Fu L., Yang Z.J., Chen S.Y., Wang J., Lai S.J. 2014. Investigation of JAK1 and STAT3 polymorphisms and their gene-gene interactions in nonspecific digestive disorder of rabbits. Gene, 543: 8-14.

Fu L., Zhao M.D., Chen S.Y., Jia X.B., Lai S.J. 2015. Investigation of genetic susceptibility to nonspecific digestive disorder between TYK2, JAK1, and STAT3 genes in rabbits. Livest. Sci., 181: 137-142.

Garreau H., Eady S.J., Hurtaud J., Legarra A. 2008. Genetic parameters of production traits and resistance to digestive disorders in a commercial rabbit population. 9th World Rabbit Congress, June 10-13, 2008, Verona-Italy, 103-108.

Ghorpade D.S., Sinha A.Y., Holla S., Singh, V., Balaji K.N. 2013. NOD2-Nitric Oxide-responsive MicroRNA-146a Activates Sonic Hedgehog Signaling to Orchestrate Inflammatory Responses in Murine Model of Inflammatory Bowel Disease. J. Biol. Chem., 288: 33037-33048.

Gidenne T., Pinheiro V., Cunha L.F.E. 2000. A comprehensive approach of the rabbit digestion: consequences of a reduction in dietary fibre supply. Livest. Prod. Scie., 64: 225-237.

Haasz R., Algom D., Richter M. 1974. Cells involved in cellmediated and transplantation immunity in the rabbit. VII. The organ source(s) of the cells of the sensitized rabbit capable of transferring the delayed hypersensitivity state to allogeneic rabbits. Laboratory investigation; a journal of technical methods and pathology, 31: 60-67.

Kalla R., Ventham N.T., Kennedy N.A., Quintana J.F., Nimmo E.R., Buck A.H., Satsangi J. 2015. MicroRNAs: new players in IBD. Gut, 64: 504-517.

Koukos G., Polytarchou C., Kaplan J.L., Morley-Fletcher A., Gras-Miralles B., Kokkotou E., Baril-Dore M., Pothoulakis C., Winter H.S., Iliopoulos D. 2013. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology, 145: 842-852 e842.

Li S.C., Liao Y.L., Chan W.C., Ho M.R., Tsai K.W., Hu L.Y., Lai C.H., Hsu C.N., Lin W.C. 2011. Interrogation of rabbit miRNAs and their isomiRs. Genomics, 98: 453-459.

Liu Y.F., Zhang G.W., Xiao Z.L., Yang Y., Deng X.S., Chen S.Y., Wang J., Lai S.J. 2013. Single Nucleotide Polymorphisms of NLRP12 Gene and Association with Non-specific Digestive Disorder in Rabbit. Asian-Austral. J. Anim., 26: 1072-1079.

Lockshin R.A., Zakeri Z. 2004. Apoptosis, autophagy, and more. Int. J. Biochem. Cell B., 36: 2405-2419.

Lu C., Chen J., Xu H.G., Zhou X., He Q., Li Y.L., Jiang G., Shan Y., Xue B., Zhao R.X., Wang Y., Werle K.D., Cui R., Liang J., Xu Z.X. 2014. MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy. Gastroenterology, 146: 188-199.

Marai I.F., Askar A., Mckroskey R.A., Tena E. 2010. Replacement in rabbit herds: a review. Trop. Subtrop. Agroecosyst., 12: 431-444.

Nata T., Fujiya M., Ueno N., Moriichi K., Konishi H., Tanabe H., Ohtake T., Ikuta K., Kohgo Y. 2013. MicroRNA-146b improves intestinal injury in mouse colitis by activating nuclear factor-κB and improving epithelial barrier function. J. Gene Med., 15: 249-260.

Nguyen H.T., Dalmasso G., Müller S., Carrière J., Seibold F., Darfeuille-Michaud A. 2014. Crohn’s disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy. Gastroenterology, 146: 508-519.

Salim S.Y., Söderholm J.D. 2011. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm. Bowel Dis., 17: 362-381.

Sharma A., Kumar M., Aich J., Hariharan M., Brahmachari S.K., Agrawal A., Ghosh B. 2009. Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a. In Proc.: National Academy of Sciences of the United States of America, 106: 5761-5766.

Yang Y., Ma Y., Shi C., Chen H., Zhang H., Chen N., Zhang P., Wang F., Yang J., Yang J., Zhu Q., Liang Y., Wu W., Gao R., Yang Z., Zou Y., Qin H. 2013a. Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB. Biochemical and biophysical research communications, 434: 746-752.

Yang Y., Zhang G.W., Chen S.Y., Peng J., Lai S.J. 2013b. Polymorphism of NLRP3 Gene and Association with Susceptibility to Digestive Disorders in Rabbit. Asian-Australasian journal of animal sciences, 26: 455-462.

Zhai Z., Wu F., Dong F., Chuang A.Y., Messer J.S., Boone D.L., Kwon J.H. 2014. Human autophagy gene ATG16L1 is posttranscriptionally regulated by MIR142-3p. Autophagy, 10: 468-479.

Zhang G.W., Wang H.Z., Chen S.Y., Li Z.C., Zhang W.X., Lai S.J. 2011. A reduced incidence of digestive disorders in rabbits is associated with allelic diversity at the TLR4 locus. Vet. Immunol. Immunop., 144: 482-486.

Zhang W.X., Zhang G.W., Peng J., Zhang J.L., Yang Y., Lai S.J. 2013. A synonymous mutation in NOD2 gene was significantly associated with non-specific digestive disorder in rabbit. Gene, 516: 193-197.

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 Universitat Politècnica de València


Official journal of the World Rabbit Science Association (WRSA)


e-ISSN: 1989-8886     ISSN: 1257-5011