LncRNA DRAIC regulates cell proliferation and migration by affecting the miR-34a-5p/ITGA6 signal axis in Hirschsprung’s disease
Background: Hirschsprung’s disease (HSCR) is a common defect in newborns, and studies have revealed that long non-coding RNA (lncRNA) is involved in the progression of HSCR. This research study aims to investigate the mechanism of downregulated RNA in cancer (DRAIC) on cell proliferation and migration in HSCR.
Methods: Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) was used to detect the expression of DRAIC in HSCR bowel stenosis tissues and normal colon tissues. Cell-counting kit-8 (CCK-8) and Transwell assays were employed to explore whether cellular functions change after overexpression or knockdown of the DRAIC in SH-SY5Y cells and human 293T cells. Protein expression levels were determined by Western blot analysis. RNA pull-down and dual-luciferase reporter assays were used to confirm the competitive relationship of DRAIC and integrin subunit alpha 6 (ITGA6) through their association with miR-34a-5p.
Results: The lncRNA DRAIC was significantly increased in colon tissue from HSCR patients. The overexpression of DRAIC inhibited SH-SY5Y cell and human 293T cell proliferation and migration. Knockdown of DRAIC, however, promoted cell proliferation and migration. The RNA pull-down and dual-luciferase reporter assays have proven the competitive relationship between DRAIC and ITGA6 through their association with miR-34a-5p. Further rescue experiments have confirmed that DRAIC regulates cell proliferation and migration by affecting the miR-34a-5p/ITGA6 signal axis in HSCR.
Conclusion: DRAIC promoted cell proliferation and migration by regulating the miR-34a-5p/ITGA6 signal axis in HSCR.
- Bahrami A, Joodi M, Moetamani-Ahmadi M, Maftouh M, Hassanian S, Ferns G, et al. Genetic background of Hirschsprung disease: a bridge between basic science and clinical application. J Cell Biochem. 2018;119:28–33. doi: 10.1002/jcb.26149
- Godbole K. Many faces of Hirschsprung’s disease. Indian Pediatr. 2004;41:1115–23.
- Rogers J. Search for the missing lncs: gene regulatory networks in neural crest development and long non-coding RNA biomarkers of Hirschsprung’s disease. Neurogastroenterol Motil. 2016;28:161–6. doi: 10.1111/nmo.12776
- Torroglosa A, Villalba-Benito L, Fernández R, Luzón-Toro B, Moya-Jiménez M, Antiñolo G, et al. Identification of new potential lncRNA biomarkers in Hirschsprung disease. Int J Mol Sci. 2020;21:5534. doi: 10.3390/ijms21155534
- Li F, Zhou X, Chen M, Fan W. Regulatory effect of LncRNA DRAIC/miR-149-5p/NFIB molecular network on autophagy of esophageal cancer cells and its biological behavior. Exp Mol Pathol. 2020;116:104491. doi: 10.1016/j.yexmp.2020.104491
- Zhang Z, Hu X, Kuang J, Liao J, Yuan Q. LncRNA DRAIC inhibits proliferation and metastasis of gastric cancer cells through interfering with NFRKB deubiquitination mediated by UCHL5. Cell Mol Biol Lett. 2020;25:29. doi: 10.1186/s11658-020-00221-0
- Saha S, Kiran M, Kuscu C, Chatrath A, Wotton D, Mayo M, et al. Long noncoding RNA DRAIC inhibits prostate cancer progression by interacting with IKK to inhibit NF-κB activation. Cancer Res. 2020;80:950–63. doi: 10.1158/0008-5472.CAN-19-3460
- Niu X, Xu Y, Gao N, Li A. Weighted gene coexpression network analysis reveals the critical lncRNAs and mRNAs in development of Hirschsprung’s disease. J Comput Biol. 2020;27:1115–29. doi: 10.1089/cmb.2019.0261
- Li Y, Lv X, Chen H, Zhi Z, Wei Z, Wang B, et al. Peptide derived from AHNAK inhibits cell migration and proliferation in Hirschsprung’s disease by targeting the ERK1/2 pathway. J Proteome Res. 2021;20:2308–18. doi: 10.1021/acs.jproteome.0c00811
- Watanabe Y, Broders-Bondon F, Baral V, Paul-Gilloteaux P, Pingault V, Dufour S, et al. Sox10 and Itgb1 interaction in enteric neural crest cell migration. Dev Biol. 2013;379:92–106. doi: 10.1016/j.ydbio.2013.04.013
- Pan W, Wu A, Yu H, Yu Q, Zheng B, Yang W, et al. Involvement of the lncRNA AFAP1-AS1/microRNA-195/E2F3 axis in proliferation and migration of enteric neural crest stem cells of Hirschsprung’s disease. Exp Physiol. 2020;105:1939–49. doi: 10.1113/EP088780
- Li Y, Zhou L, Lu C, Shen Q, Su Y, Zhi Z, et al. Long non-coding RNA FAL1 functions as a ceRNA to antagonize the effect of miR-637 on the down-regulation of AKT1 in Hirschsprung’s disease. Cell Prolif. 2018;51:e12489. doi: 10.1111/cpr.12489
- Su Y, Wen Z, Shen Q, Zhang H, Peng L, Chen G, et al. Long non-coding RNA LOC100507600 functions as a competitive endogenous RNA to regulate BMI1 expression by sponging miR128-1-3p in Hirschsprung’s disease. Cell Cycle. 2018;17:459-67. doi: 10.1080/15384101.2017.1403688
- Samadian M, Gholipour M, Hajiesmaeili M, Taheri M, Ghafouri-Fard S. The eminent role of microRNAs in the pathogenesis of Alzheimer’s disease. Front Aging Neurosci. 2021;13:641080. doi: 10.3389/fnagi.2021.641080
- Wegner S, Uhlemann R, Boujon V, Ersoy B, Endres M, Kronenberg G, et al. Endothelial cell-specific transcriptome reveals signature of chronic stress related to worse outcome after mild transient brain ischemia in mice. Mol Neurobiol. 2020;57:1446–58. doi: 10.1007/s12035-019-01822-3
- Fan H, Yuan F, Yun Y, Wu T, Lu L, Liu J, et al. MicroRNA-34a mediates ethanol-induced impairment of neural differentiation of neural crest cells by targeting autophagy-related gene 9a. Exp Neurol. 2019;320:112981. doi: 10.1016/j.expneurol.2019.112981
- Gao J, Li N, Dong Y, Li S, Xu L, Li X, et al. MiR-34a-5p suppresses colorectal cancer metastasis and predicts recurrence in patients with stage II/III colorectal cancer. Oncogene. 2015;34:4142–52. doi: 10.1038/onc.2014.348
- Li S, Zhu K, Liu L, Gu J, Niu H, Guo J. LncARSR sponges miR-34a-5p to promote colorectal cancer invasion and metastasis via hexokinase-1-mediated glycolysis. Cancer Sci. 2020;111:3938–52. doi: 10.1111/cas.14617
- Cai P, Li H, Huo W, Zhu H, Xu C, Zang R, et al. Aberrant expression of LncRNA-MIR31HG regulates cell migration and proliferation by affecting miR-31 and miR-31* in Hirschsprung’s disease. J Cell Biochem. 2018;119:8195–203. doi: 10.1002/jcb.26830
- Shen Z, Peng L, Zhu Z, Xie H, Zang R, Du C, et al. Downregulated expression of long non-coding RNA LOC101926975 impairs both cell proliferation and cell cycle and its clinical implication in Hirschsprung disease patients. Int J Med Sci. 2016;13:292–7. doi: 10.7150/ijms.14187
- Liao B, Wang Z, Zhu Y, Wang M, Liu Y. Long noncoding RNA DRAIC acts as a microRNA-122 sponge to facilitate nasopharyngeal carcinoma cell proliferation, migration and invasion via regulating SATB1. Artif Cells Nanomed Biotechnol. 2019;47:3585–97. doi: 10.1080/21691401.2019.1656638
- Xu X, Peng X, Yin X, Liu Y, Shi Z. MiR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation. Acta Histochem. 2020;122:151576. doi: 10.1016/j.acthis.2020.151576
- Zheng F, Li J, Ma C, Tang X, Tang Q, Wu J, et al. Novel regulation of miR-34a-5p and HOTAIR by the combination of berberine and gefitinib leading to inhibition of EMT in human lung cancer. J Cell Mol Med. 2020;24:5578–92. doi: 10.1111/jcmm.15214
- Li H, Duan Y, Zhao N. MiR-34a-5p directly targeting TRIM44 affects the biological behavior of ovarian cancer cells. Eur Rev Med Pharmacol Sci. 2021;25:1250–60. doi: 10.26355/eurrev_202102_24829
- Tu Y, Ma T, Wen T, Yang T, Xue L, Cai M, et al. MicroRNA-377-3p alleviates IL-1β-caused chondrocyte apoptosis and cartilage degradation in osteoarthritis in part by downregulating ITGA6. Biochem Biophys Res Commun. 2020;523:46–53. doi: 10.1016/j.bbrc.2019.11.186
- Guo L, Fu J, Sun S, Zhu M, Zhang L, Niu H, et al. MicroRNA-143-3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3. Cancer Sci. 2019;110:805–16. doi: 10.1111/cas.13910
- Zhu Y, Wu Y, Yang L, Dou X, Jiang J, Wang L. Long non-coding RNA activated by transforming growth factor-β promotes proliferation and invasion of cervical cancer cells by regulating the miR-144/ITGA6 axis. Exp Physiol. 2019;104:837–44. doi: 10.1113/EP087656
- Yang J, Jiang B, Hai J, Duan S, Dong X, Chen C. Long noncoding RNA opa-interacting protein 5 antisense transcript 1 promotes proliferation and invasion through elevating integrin α6 expression by sponging miR-143-3p in cervical cancer. J Cell Biochem. 2019;120:907–16. doi: 10.1002/jcb.27454
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright of their work, with first publication rights granted to Upsala Mecical Society. Read the full Copyright- and Licensing Statement.