Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2021, Vol. 35 ›› Issue (6): 132-137.doi: 10.6040/j.issn.1673-3770.0.2021.096

Previous Articles     Next Articles

Research progress of miRNA-29b involved in EMT-related signaling pathway regulation

WANG Junxin1,2,SUN Yan2   

  1. 1. College of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Otorhinolaryngology & Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University / Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai 264000, Shandong, China
  • Published:2021-12-10

PDF (PC)

241

Abstract: Epithelial-mesenchymal transition(EMT)is a biological process of epithelial cells transforming into mesenchymal cells, conferring the ability of cell metastasis and invasion. This process is closely related to the progression of organ fibrosis and tumors. MiRNA-29b is a small noncoding RNA closely related to the EMT process. By modulating TGF-β/Smad, PI3K/AKT, Wnt/β-catenin, and other signaling pathways, miRNA-29b mediates the development of type II and type III EMT, and then delays the process of organ fibrosis, regulates the invasion and metastasis of tumors. The targeted therapy of miRNA-29b is expected to provide a new perspective for the clinical diagnosis and treatment of organ fibrosis and tumor invasion and metastasis. The research status of miRNA-29b regulating the process of organ fibrosis and tumor invasion and metastasis through various EMT-related signaling pathways was reviewed in this study.

Key words: MiRNA-29b, Epithelial-mesenchymal transition, Organ fibrosis, Tumor invasion and metastasis, Signaling pathway

CLC Number: 

  • R762
[1] Yang J, Antin P, Berx G, et al. Guidelines and definitions for research on epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2020, 21(6): 341-352. doi:10.1038/s41580-020-0237-9.
[2] Kim DH, Xing TS, Yang ZB, et al. Epithelial mesenchymal transition in embryonic development, tissue repair and cancer: a comprehensive overview[J]. J Clin Med, 2017, 7(1): E1. doi:10.3390/jcm7010001.
[3] Razali RA, Lokanathan Y, Yazid MD, et al. Modulation of epithelial to mesenchymal transition signaling pathways by olea europaea and its active compounds[J]. Int J Mol Sci, 2019, 20(14). doi: 10.3390/ijms20143492.
[4] Lee RC, Feinbaum RL, Ambros V. The c elegans heterochronic gene Lin-4 encodes small RNAs with antisense complementarity to Lin-14[J]. Cell, 1993, 75(5): 843-854. doi:10.1016/0092-8674(93)90529-y.
[5] 谢益, 韩锋产. miRNAs与内耳发育和听觉毛细胞凋亡与再生的研究进展[J]. 山东大学耳鼻喉眼学报, 2019,33(2): 126-129. doi: 10.6040/j.issn.1673-3770.0.2018.268. XIE Yi, HAN Fengchan. Role of miRNAs in inner ear development and apoptosis or regeneration of auditory hair cells[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019,33(2): 126-129. doi: 10.6040/j.issn.1673-3770.0.2018.268.
[6] Lagos-Quintana M, Rauhut R, Lendeckel W, et al. Identification of novel genes coding for small expressed RNAs[J]. Science, 2001, 294(5543): 853-858. doi:10.1126/science.1064921.
[7] Alizadeh M, Safarzadeh A, Beyranvand F, et al. The potential role of miR-29 in health and cancer diagnosis, prognosis, and therapy[J]. J Cell Physiol, 2019, 234(11): 19280-19297. doi:10.1002/jcp.28607.
[8] Hanna A, Humeres C, Frangogiannis NG. The role of Smad signaling cascades in cardiac fibrosis[J]. Cell Signal, 2021, 77: 109826. doi:10.1016/j.cellsig.2020.109826.
[9] Gu YY, Liu XS, Huang XR, et al. Diverse role of TGF-β in kidney disease[J]. Front Cell Dev Biol, 2020, 8: 123. doi:10.3389/fcell.2020.00123.
[10] Ma J, Sanchez-Duffhues G, Goumans MJ, et al. TGF-β-induced endothelial to mesenchymal transition in disease and tissue engineering[J]. Front Cell Dev Biol, 2020, 8: 260. doi:10.3389/fcell.2020.00260.
[11] Hu HH, Chen DQ, Wang YN, et al. New insights into TGF-β/Smad signaling in tissue fibrosis[J]. Chem Biol Interact, 2018, 292: 76-83. doi:10.1016/j.cbi.2018.07.008.
[12] Yu JW, Duan WJ, Huang XR, et al. MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis[J]. Lab Invest, 2014, 94(9): 978-990. doi:10.1038/labinvest.2014.91.
[13] Wang T, Li Y, Chen J, et al. TGF-β1/Smad3 signaling promotes collagen synthesis in pulmonary artery smooth muscle by down-regulating miR-29b[J]. International journal of clinical and experimental pathology, 2018, 11(12): 5592-5601. PMID: 31949646
[14] Zhang Y, Huang XR, Wei LH, et al. miR-29b as a therapeutic agent for angiotensin II-induced cardiac fibrosis by targeting TGF-β/Smad3 signaling[J]. Mol Ther, 2014, 22(5): 974-985. doi:10.1038/mt.2014.25.
[15] Li LR, Ren SH, Hao XD, et al. MicroRNA-29b inhibits human vascular smooth muscle cell proliferation via targeting the TGF-β/Smad3 signaling pathway[J]. Exp Ther Med, 2021, 21(5): 492. doi:10.3892/etm.2021.9923.
[16] Liang C, Bu S, Fan X. Suppressive effect of microRNA-29b on hepatic stellate cell activation and its crosstalk with TGF-β1/Smad3[J]. Cell Biochem Funct, 2016, 34(5): 326-333. doi:10.1002/cbf.3193.
[17] Li JX, Du SH, Sheng XJ, et al. MicroRNA-29b inhibits endometrial fibrosis by regulating the Sp1-TGF-β1/smad-CTGF axis in a rat model[J]. Reprod Sci, 2016, 23(3): 386-394. doi:10.1177/1933719115602768.
[18] Guo JD, Lin Q, Shao Y, et al. miR-29b promotes skin wound healing and reduces excessive scar formation by inhibition of the TGF-β1/Smad/CTGF signaling pathway[J]. Can J Physiol Pharmacol, 2017, 95(4): 437-442. doi:10.1139/cjpp-2016-0248.
[19] Strippoli R, Moreno-Vicente R, Battistelli C, et al. Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis[J]. Stem Cells Int, 2016. doi: 10.1155/2016/3543678.
[20] Li N, Cui JL, Duan XC, et al. Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway in human tenon's fibroblasts[J]. Invest Ophthalmol Vis Sci, 2012, 53(3): 1670. doi:10.1167/iovs.11-8670.
[21] Yu J, Luo HM, Li N, et al. Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway, part II: an in vivo investigation[J]. Invest Ophthalmol Vis Sci, 2015, 56(10): 6019-6028. doi:10.1167/iovs.15-16558.
[22] Wang J, Chu ES, Chen HY, et al. microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway[J]. Oncotarget, 2015, 6(9): 7325-7338. doi:10.18632/oncotarget.2621.
[23] Hu HT, Hu S, Xu S, et al. miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway[J]. Int J Mol Med, 2018, 42(1): 453-460. doi:10.3892/ijmm.2018.3579.
[24] Kumar P, Raeman R, Chopyk DM, et al. Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(10): 3537-3545. doi:10.1016/j.bbadis.2018.08.012.
[25] Yu F, Chen B, Dong P, et al. HOTAIR epigenetically modulates PTEN expression via MicroRNA-29b: a novel mechanism in regulation of liver fibrosis[J]. Mol Ther, 2017, 25(1): 205-217. doi:10.1016/j.ymthe.2016.10.015.
[26] Zuo YY, Liu YH. New insights into the role and mechanism of Wnt/β-catenin signalling in kidney fibrosis[J]. Nephrology(Carlton), 2018, 23(4): 38-43. doi:10.1111/nep.13472.
[27] Wang YC, Liu JS, Chen JY, et al. MiR-29 mediates TGFβ 1-induced extracellular matrix synthesis through activation of Wnt/β -catenin pathway in human pulmonary fibroblasts[J]. Technol Health Care, 2015, 23(1): S119-S125. doi:10.3233/thc-150943.
[28] Zhang H, Chen J, Shen ZY, et al. Indoxyl sulfate accelerates vascular smooth muscle cell calcification via microRNA-29b dependent regulation of Wnt/β-catenin signaling[J]. Toxicol Lett, 2018, 284: 29-36. doi:10.1016/j.toxlet.2017.11.033.
[29] Ding DY, Li CF, Zhao TC, et al. LncRNA H19/miR-29b-3p/PGRN axis promoted epithelial-mesenchymal transition of colorectal cancer cells by acting on wnt signaling[J]. Mol Cells, 2018, 41(5): 423-435. doi:10.14348/molcells.2018.2258.
[30] Liu W, Ruan T, Ji X, et al. The Gli1-Snail axis contributes to Salmonella Typhimurium-induced disruption of intercellular junctions of intestinal epithelial cells[J]. Cell Microbiol, 2020, 22(8): e13211. doi:10.1111/cmi.13211.
[31] Cui L, Zhang Y, Ge X, et al. Downregulated PEG3 ameliorates cardiac fibrosis and myocardial injury in mice with ischemia/reperfusion through the NF-κB signaling pathway[J]. J Bioenerg Biomembr, 2020, 52(3): 143-154. doi:10.1007/s10863-020-09831-x.
[32] Zhang JY, Zeng Y, Chen JW, et al. miR-29a/b cluster suppresses high glucose-induced endothelial-mesenchymal transition in human retinal microvascular endothelial cells by targeting Notch2[J]. Exp Ther Med, 2019, 17(4): 3108-3116. doi:10.3892/etm.2019.7323.
[33] Wang Y, Zeng ZS, Guan L, et al. GRHL2 induces liver fibrosis and intestinal mucosal barrier dysfunction in non-alcoholic fatty liver disease via microRNA-200 and the MAPK pathway[J]. J Cell Mol Med, 2020, 24(11): 6107-6119. doi:10.1111/jcmm.15212.
[34] Stemmler MP, Eccles RL, Brabletz S, et al. Non-redundant functions of EMT transcription factors[J]. Nat Cell Biol, 2019, 21(1): 102-112. doi:10.1038/s41556-018-0196-y.
[35] Shi C, Rao C, Sun C, et al. miR-29s function as tumor suppressors in gliomas by targeting TRAF4 and predict patient prognosis[J]. Cell Death Dis, 2018, 9(11): 1078. doi:10.1038/s41419-018-1092-x.
[36] Koshizuka K, Kikkawa N, Hanazawa T, et al. Inhibition of integrin β1-mediated oncogenic signalling by the antitumor microRNA-29 family in head and neck squamous cell carcinoma[J]. Oncotarget, 2018, 9(3): 3663-3676. doi:10.18632/oncotarget.23194.
[37] Manikandan M, Deva Magendhra Rao AK, Arunkumar G, et al. Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism[J]. Mol Cancer, 2016, 15: 28. doi:10.1186/s12943-016-0512-8.
[38] Kurihara-Shimomura M, Sasahira T, Shimomura H, et al. The oncogenic activity of miR-29b-1-5p induces the epithelial-mesenchymal transition in oral squamous cell carcinoma[J]. J Clin Med, 2019, 8(2): 273. doi:10.3390/jcm8020273.
[39] Duhachek-Muggy S, Zolkiewska A. ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer[J]. BMC Cancer, 2015, 15: 93. doi:10.1186/s12885-015-1108-1.
[40] Drago-Ferrante R, Pentimalli F, Carlisi D, et al. Suppressive role exerted by microRNA-29b-1-5p in triple negative breast cancer through SPIN1 regulation[J]. Oncotarget, 2017, 8(17): 28939-28958. doi:10.18632/oncotarget.15960.
[41] To SKY, Mak ASC, Eva Fung YM, et al. Β-catenin downregulates Dicer to promote ovarian cancer metastasis[J]. Oncogene, 2017, 36(43): 5927-5938. doi:10.1038/onc.2017.185.
[42] Yuan L, Zhou C, Lu YX, et al. IFN-γ-mediated IRF1/miR-29b feedback loop suppresses colorectal cancer cell growth and metastasis by repressing IGF1[J]. Cancer Lett, 2015, 359(1): 136-147. doi:10.1016/j.canlet.2015.01.003.
[43] Leng Y, Chen ZX, Ding H, et al. Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis[J]. Cancer Cell Int, 2021, 21(1): 17. doi:10.1186/s12935-020-01700-2.
[44] Musavi Shenas SMH, Mansoori B, Mohammadi A, et al. SiRNA-mediated silencing of Snail-1 induces apoptosis and alters micro RNA expression in human urinary bladder cancer cell line[J]. Artif Cells Nanomed Biotechnol, 2017, 45(5): 969-974. doi:10.1080/21691401.2016.1198361.
[45] Lv M, Zhong ZY, Huang MG, et al. lncRNA H19 regulates epithelial-mesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA[J]. Biochim Biophys Acta Mol Cell Res, 2017, 1864(10): 1887-1899. doi:10.1016/j.bbamcr.2017.08.001.
[1] HUANG Danyi, ZHANG Ting,CHEN Jing, ZHANG Wei. Progress of research regarding the role of the epithelial barrier in chronic rhinosinusitis with nasal polyps [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 78-83.
[2] ZHANG Yaqi, LIU Huimin, CAO Linman, WANG Ziyu, LIN Xu, LI Yanping, XUE Gang, WU Jingfang. Expression and significance of the MAPK,PI3K-AKT,NF-κB pathways of allergic rhinitis in mice [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 254-259.
[3] LIU Yong, YUAN Cunli, CAO Hui, ZHENG Chengcai, CHAO Fang, XU Fenglei. CHD1L promotes proliferation, invasion and metastasis of laryngeal squamous cell carcinoma cells by EMT [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(2): 32-39.
[4] LI Guobin, ZHANG Zhancheng, WANG Xinyan. Up-regulation of miR-200b may inhibit epithelial mesenchymal transition process to prevent the proliferation, migration, and invasion of human laryngeal cancer Hep-2 cells [J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(4): 53-57.
[5] WANG Hui, WEN Yan, YAN Li, YU Xiaoming, NING Hong. The effect of transforming growth factor-β1 on epithelial-mesenchymal transition in human lens epithelial cells. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(4): 76-79.
[6] GUO Zhi-juan1, LI Pei-hua1, ZHANG Xiao-wen2. Prognostic significance of epithelial-mesenchymal transition state in patients with chronic sinusitis treated under endoscopy [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2014, 28(1): 34-38.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(2): 116 -118 .
[2] ZHOU Zi-ning,JIN Guo-wei . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(5): 462 -465 .
[3] ZHOU Bin,LI Bin . Endoscopic sinus surgery for 75 patients with chronic sinusitis and nasal polyps[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 24 -26 .
[4] XU Sainan,YANG Lei . Apoptosis of epithelial cells in nasal polyps promoted by erythromycin[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 27 -29 .
[5] . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(1): 94 -95 .
[6] LIU Lian-he . Treatment of deep neck abscess in 37 cases[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(2): 180 -181 .
[7] . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(3): 200 -203 .
[8] QIAO Yi,NI Guan-sen,CHEN Wen-wen . Effect of H-UPPP and nasal operations on obstructive sleep apnea syndrome in 38 cases
[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(3): 206 -208 .
[9] WANG Xiao-feng,LIN Chang,CHENG Jin-mei . Expression of ABAD in inner ears and its clinical significance in different age mice[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(3): 207 -211 .
[10] FAN Qi-jun,HUANG Zhi-wu,MEI Ling,XIAO Bo-kui . Expression of the heat shock protein 27 in rat cochlea induced by sodium salicylate injection by the FQ-PCR technique[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(3): 212 -214 .
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd