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http://dx.doi.org/10.12701/yujm.2020.00836

The role of microRNAs in cell death pathways  

Jang, Ji Hoon (Department of Anatomy, Yeungnam University College of Medicine)
Lee, Tae-Jin (Department of Anatomy, Yeungnam University College of Medicine)
Publication Information
Journal of Yeungnam Medical Science / v.38, no.2, 2021 , pp. 107-117 More about this Journal
Abstract
MicroRNAs (miRNAs) are a class of noncoding RNAs that negatively regulate target messenger RNAs. In multicellular eukaryotes, numerous miRNAs perform basic cellular functions, including cell proliferation, differentiation, and death. Abnormal expression of miRNAs weakens or modifies various apoptosis pathways, leading to the development of human cancer. Cell death occurs in an active manner that maintains tissue homeostasis and eliminates potentially harmful cells through regulated cell death processes, including apoptosis, autophagic cell death, and necroptosis. In this review, we discuss the involvement of miRNAs in regulating cell death pathways in cancers and the potential therapeutic functions of miRNAs in cancer treatment.
Keywords
Apoptosis; Autophagy; Endoplasmic reticulum stress; MicroRNAs; Necroptosis;
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1 Zhang J, Du Y, Wu C, Ren X, Ti X, Shi J, et al. Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway. Oncol Rep 2010;24:1217-23.
2 Corazzari M, Gagliardi M, Fimia GM, Piacentini M. Endoplasmic reticulum stress, unfolded protein response, and cancer cell fate. Front Oncol 2017;7:78.   DOI
3 Lambertz I, Nittner D, Mestdagh P, Denecker G, Vandesompele J, Dyer MA, et al. Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. Cell Death Differ 2010;17:633-41.   DOI
4 Bae J, Donigian JR, Hsueh AJ. Tankyrase 1 interacts with Mcl-1 proteins and inhibits their regulation of apoptosis. J Biol Chem 2003;278:5195-204.   DOI
5 Huang X, Xiao S, Zhu X, Yu Y, Cao M, Zhang X, et al. miR196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling. Cell Death Dis 2020;11:785.   DOI
6 Hiramatsu N, Chiang K, Aivati C, Rodvold JJ, Lee JM, Han J, et al. PERK-mediated induction of microRNA-483 disrupts cellular ATP homeostasis during the unfolded protein response. J Biol Chem 2020;295:237-49.   DOI
7 Degenhardt K, Mathew R, Beaudoin B, Bray K, Anderson D, Chen G, et al. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell 2006;10:51-64.   DOI
8 Callegari E, D'Abundo L, Guerriero P, Simioni C, Elamin BK, Russo M, et al. miR-199a-3p modulates MTOR and PAK4 pathways and inhibits tumor growth in a hepatocellular carcinoma transgenic mouse model. Mol Ther Nucleic Acids 2018;11:485-93.   DOI
9 An Y, Zhang Z, Shang Y, Jiang X, Dong J, Yu P, et al. miR-23b3p regulates the chemoresistance of gastric cancer cells by targeting ATG12 and HMGB2. Cell Death Dis 2015;6:e1766.   DOI
10 Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, Huang J, et al. miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer Res 2012;72:3631-41.   DOI
11 Favreau AJ, Shaffiey F, Cross E, Sathyanarayana P. Mir-590 is a novel STAT5 regulated oncogenic miRNA and targets FasL in acute myeloid leukemia. Blood 2013;122:3811.   DOI
12 Wang P, Zhuang L, Zhang J, Fan J, Luo J, Chen H, et al. The serum miR-21 level serves as a predictor for the chemosensitivity of advanced pancreatic cancer, and miR-21 expression confers chemoresistance by targeting FasL. Mol Oncol 2013;7:334-45.   DOI
13 Wang HQ, Yu XD, Liu ZH, Cheng X, Samartzis D, Jia LT, et al. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol 2011;225:232-42.   DOI
14 Iwamaru A, Kondo Y, Iwado E, Aoki H, Fujiwara K, Yokoyama T, et al. Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells. Oncogene 2007;26:1840-51.   DOI
15 Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017;168:960-76.   DOI
16 Rabanal-Ruiz Y, Otten EG, Korolchuk VI. mTORC1 as the main gateway to autophagy. Essays Biochem 2017;61:565-84.   DOI
17 Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 2011;12:99-110.   DOI
18 Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis 2015;35:3-11.   DOI
19 Acunzo M, Romano G, Wernicke D, Croce CM. MicroRNA and cancer: a brief overview. Adv Biol Regul 2015;57:1-9.   DOI
20 Maziere P, Enright AJ. Prediction of microRNA targets. Drug Discov Today 2007;12:452-8.   DOI
21 Jo MH, Shin S, Jung SR, Kim E, Song JJ, Hohng S. Human Argonaute 2 has diverse reaction pathways on target RNAs. Mol Cell 2015;59:117-24.   DOI
22 Su Z, Yang Z, Xu Y, Chen Y, Yu Q. MicroRNAs in apoptosis, autophagy and necroptosis. Oncotarget 2015;6:8474-90.   DOI
23 Zhao G, Zhang JG, Liu Y, Qin Q, Wang B, Tian K, et al. miR148b functions as a tumor suppressor in pancreatic cancer by targeting AMPKα1. Mol Cancer Ther 2013;12:83-93.   DOI
24 Yin H, Ma J, Chen L, Piao S, Zhang Y, Zhang S, et al. miR-99a enhances the radiation sensitivity of non-small cell lung cancer by targeting mTOR. Cell Physiol Biochem 2018;46:471-81.   DOI
25 Yu T, Li J, Yan M, Liu L, Lin H, Zhao F, et al. MicroRNA-193a3p and -5p suppress the metastasis of human non-small-cell lung cancer by downregulating the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway. Oncogene 2015;34:413-23.   DOI
26 Ge H, Li B, Hu WX, Li RJ, Jin H, Gao MM, et al. MicroRNA-148b is down-regulated in non-small cell lung cancer and associated with poor survival. Int J Clin Exp Pathol 2015;8:800-5.
27 Li H, Wang Y, Song Y. MicroRNA-26b inhibits the immune response to Mycobacterium tuberculosis (M.tb) infection in THP-1 cells via targeting TGFβ-activated kinase-1 (TAK1), a promoter of the NF-κB pathway. Int J Clin Exp Pathol 2018; 11:1218-27.
28 Huang G, Nishimoto K, Zhou Z, Hughes D, Kleinerman ES. miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Res 2012;72:908-16.   DOI
29 Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35:495-516.   DOI
30 Ali Syeda Z, Langden SS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci 2020;21:1723.   DOI
31 Yin W, Chen J, Wang G, Zhang D. MicroRNA-106b functions as an oncogene and regulates tumor viability and metastasis by targeting LARP4B in prostate cancer. Mol Med Rep 2019;20:951-8.
32 Curtale G, Citarella F, Carissimi C, Goldoni M, Carucci N, Fulci V, et al. An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood 2010;115:265-73.   DOI
33 Razumilava N, Bronk SF, Smoot RL, Fingas CD, Werneburg NW, Roberts LR, et al. miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma. Hepatology 2012;55:465-75.   DOI
34 Yamada N, Noguchi S, Kumazaki M, Shinohara H, Miki K, Naoe T, et al. Epigenetic regulation of microRNA-128a expression contributes to the apoptosis-resistance of human T-cell leukaemia jurkat cells by modulating expression of fas-associated protein with death domain (FADD). Biochim Biophys Acta 2014;1843:590-602.   DOI
35 Melet A, Song K, Bucur O, Jagani Z, Grassian AR, Khosravi-Far R. Apoptotic pathways in tumor progression and therapy. Adv Exp Med Biol 2008;615:47-79.   DOI
36 Fulda S, Debatin KM. Targeting inhibitor of apoptosis proteins (IAPs) for diagnosis and treatment of human diseases. Recent Pat Anticancer Drug Discov 2006;1:81-9.   DOI
37 Fulda S. Targeting c-FLICE-like inhibitory protein (CFLAR) in cancer. Expert Opin Ther Targets 2013;17:195-201.   DOI
38 Czochor JR, Glazer PM. MicroRNAs in cancer cell response to ionizing radiation. Antioxid Redox Signal 2014;21:293-312.   DOI
39 Korkmaz G, le Sage C, Tekirdag KA, Agami R, Gozuacik D. miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy 2012;8:165-76.   DOI
40 Green DR, Llambi F. Cell death signaling. Cold Spring Harb Perspect Biol 2015;7:a006080.   DOI
41 Lavrik I, Golks A, Krammer PH. Death receptor signaling. J Cell Sci 2005;118(Pt 2):265-7.   DOI
42 Debatin KM, Krammer PH. Death receptors in chemotherapy and cancer. Oncogene 2004;23:2950-66.   DOI
43 Lamkanfi M, Declercq W, Kalai M, Saelens X, Vandenabeele P. Alice in caspase land. A phylogenetic analysis of caspases from worm to man. Cell Death Differ 2002;9:358-61.   DOI
44 Gerspach J, Pfizenmaier K, Wajant H. Therapeutic targeting of CD95 and the TRAIL death receptors. Recent Pat Anticancer Drug Discov 2011;6:294-310.   DOI
45 Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C, Kroemer G. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 2006;13:1423-33.   DOI
46 Fulda S, Debatin KM. Targeting apoptosis pathways in cancer therapy. Curr Cancer Drug Targets 2004;4:569-76.   DOI
47 Walters J, Pop C, Scott FL, Drag M, Swartz P, Mattos C, et al. A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis. Biochem J 2009;424:335-45.   DOI
48 Natoni F, Diolordi L, Santoni C, Gilardini Montani MS. Sodium butyrate sensitises human pancreatic cancer cells to both the intrinsic and the extrinsic apoptotic pathways. Biochim Biophys Acta 2005;1745:318-29.   DOI
49 Zhang X, Zhang X, Hu S, Zheng M, Zhang J, Zhao J, et al. Identification of miRNA-7 by genome-wide analysis as a critical sensitizer for TRAIL-induced apoptosis in glioblastoma cells. Nucleic Acids Res 2017;45:5930-44.   DOI
50 Upton JP, Austgen K, Nishino M, Coakley KM, Hagen A, Han D, et al. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol 2008;28:3943-51.   DOI
51 Gozuacik D, Akkoc Y, Ozturk DG, Kocak M. Autophagy-regulating microRNAs and cancer. Front Oncol 2017;7:65.
52 Fu Z, Luo W, Wang J, Peng T, Sun G, Shi J, et al. Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma. Biochem Biophys Res Commun 2017;492:480-6.   DOI
53 Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, et al. VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell 2012;21:532-46.   DOI
54 Zhang S, Gao L, Thakur A, Shi P, Liu F, Feng J, et al. miRNA-204 suppresses human non-small cell lung cancer by targeting ATF2. Tumour Biol 2016;37:11177-86.   DOI
55 Sun T, Li MY, Li PF, Cao JM. MicroRNAs in cardiac autophagy: small molecules and big role. Cells 2018;7:104.   DOI
56 Zhao Y, Wang Z, Zhang W, Zhang L. MicroRNAs play an essential role in autophagy regulation in various disease phenotypes. Biofactors 2019;45:844-56.   DOI
57 Menghini R, Casagrande V, Marino A, Marchetti V, Cardellini M, Stoehr R, et al. miR-216a: a link between endothelial dysfunction and autophagy. Cell Death Dis 2014;5:e1029.   DOI
58 Baritaud M, Cabon L, Delavallee L, Galan-Malo P, Gilles ME, Brunelle-Navas MN, et al. AIF-mediated caspase-independent necroptosis requires ATM and DNA- PK-induced histone H2AX Ser139 phosphorylation. Cell Death Dis 2012;3:e390.   DOI
59 Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 1997;388:300-4.   DOI
60 Byrd AE, Aragon IV, Brewer JW. MicroRNA-30c-2* limits expression of proadaptive factor XBP1 in the unfolded protein response. J Cell Biol 2012;196:689-98.   DOI
61 Saha S, Panigrahi DP, Patil S, Bhutia SK. Autophagy in health and disease: a comprehensive review. Biomed Pharmacother 2018;104:485-95.   DOI
62 Liu B, Li J, Cairns MJ. Identifying miRNAs, targets and functions. Brief Bioinform 2014;15:1-19.   DOI
63 Ye H, Liu X, Lv M, Wu Y, Kuang S, Gong J, et al. MicroRNA and transcription factor co-regulatory network analysis reveals miR19 inhibits CYLD in T-cell acute lymphoblastic leukemia. Nucleic Acids Res 2012;40:5201-14.   DOI
64 Chen F, Zhu HH, Zhou LF, Wu SS, Wang J, Chen Z. Inhibition of c-FLIP expression by miR-512-3p contributes to taxol-induced apoptosis in hepatocellular carcinoma cells. Oncol Rep 2010;23:1457-62.
65 Ma X, Conklin DJ, Li F, Dai Z, Hua X, Li Y, et al. The oncogenic microRNA miR-21 promotes regulated necrosis in mice. Nat Commun 2015;6:7151.   DOI
66 Zeng R, Huang J, Sun Y, Luo J. Cell proliferation is induced in renal cell carcinoma through miR-92a-3p upregulation by targeting FBXW7. Oncol Lett 2020;19:3258-68.
67 Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 2009;335:1-32.   DOI
68 Grootjans S, Vanden Berghe T, Vandenabeele P. Initiation and execution mechanisms of necroptosis: an overview. Cell Death Differ 2017;24:1184-95.   DOI
69 Colell A, Ricci JE, Tait S, Milasta S, Maurer U, Bouchier-Hayes L, et al. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 2007;129:983-97.   DOI
70 Zhang X, Yao J, Guo K, Huang H, Huai S, Ye R, et al. The functional mechanism of miR-125b in gastric cancer and its effect on the chemosensitivity of cisplatin. Oncotarget 2017;9:2105-19.   DOI
71 Lin YC, Lin JF, Tsai TF, Chou KY, Chen HE, Hwang TI. Tumor suppressor miRNA-204-5p promotes apoptosis by targeting BCL2 in prostate cancer cells. Asian J Surg 2017;40:396-406.   DOI
72 Zhang Y, Schiff D, Park D, Abounader R. MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PLoS One 2014;9:e91546.   DOI
73 Xu G, Chen J, Jing G, Grayson TB, Shalev A. miR-204 targets PERK and regulates UPR signaling and β-cell apoptosis. Mol Endocrinol 2016;30:917-24.   DOI
74 English AR, Voeltz GK. Endoplasmic reticulum structure and interconnections with other organelles. Cold Spring Harb Perspect Biol 2013;5:a013227.   DOI
75 Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol 2015;10:173-94.   DOI
76 Yu B, Wen L, Xiao B, Han F, Shi Y. Single prolonged stress induces ATF6 alpha-dependent endoplasmic reticulum stress and the apoptotic process in medial frontal cortex neurons. BMC Neurosci 2014;15:115.   DOI
77 Byrd AE, Brewer JW. Micro(RNA)managing endoplasmic reticulum stress. IUBMB Life 2013;65:373-81.   DOI
78 Wang Y, Zhang S, Bao H, Mu S, Zhang B, Ma H, et al. MicroRNA-365 promotes lung carcinogenesis by downregulating the USP33/SLIT2/ROBO1 signalling pathway. Cancer Cell Int 2018;18:64.   DOI
79 Zhang WG, Chen L, Dong Q, He J, Zhao HD, Li FL, et al. Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice. Gene 2013;531:235-42.   DOI
80 Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, et al. IRE1° cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science 2012;338:818-22.   DOI
81 van den Berg A, Mols J, Han J. RISC-target interaction: cleavage and translational suppression. Biochim Biophys Acta 2008;1779:668-77.   DOI
82 Rajewsky N. MicroRNA target predictions in animals. Nat Genet 2006;38(Suppl):S8-13.   DOI
83 Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 2006;7:880-5.   DOI
84 Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, et al. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev 2009;23:2700-4.   DOI
85 Kim EA, Kim SW, Nam J, Sung EG, Song IH, Kim JY, et al. Inhibition of c-FLIPL expression by miRNA-708 increases the sensitivity of renal cancer cells to anti-cancer drugs. Oncotarget 2016;7:31832-46.   DOI
86 Park JK, Doseff AI, Schmittgen TD. MicroRNAs targeting caspase-3 and -7 in PANC-1 cells. Int J Mol Sci 2018;19:1206.   DOI
87 Li Q, Ren P, Shi P, Chen Y, Xiang F, Zhang L, et al. MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2. Anticancer Drugs 2017;28:588-95.   DOI
88 Chen Q, Xu J, Li L, Li H, Mao S, Zhang F, et al. MicroRNA-23a/b and microRNA-27a/b suppress Apaf-1 protein and alleviate hypoxia-induced neuronal apoptosis. Cell Death Dis 2014;5:e1132.   DOI
89 Zhou Y, Jia WK, Jian Z, Zhao L, Liu CC, Wang Y, et al. Downregulation of microRNA-199a-5p protects cardiomyocytes in cyanotic congenital heart disease by attenuating endoplasmic reticulum stress. Mol Med Rep 2017;16:2992-3000.   DOI
90 Kong F, Zou H, Liu X, He J, Zheng Y, Xiong L, et al. miR-7112-3p targets PERK to regulate the endoplasmic reticulum stress pathway and apoptosis induced by photodynamic therapy in colorectal cancer CX-1 cells. Photodiagnosis Photodyn Ther 2020;29:101663.   DOI
91 Behrman S, Acosta-Alvear D, Walter P. A CHOP-regulated microRNA controls rhodopsin expression. J Cell Biol 2011;192:919-27.   DOI
92 Dhuriya YK, Sharma D. Necroptosis: a regulated inflammatory mode of cell death. J Neuroinflammation 2018;15:199.   DOI
93 Chitnis NS, Pytel D, Bobrovnikova-Marjon E, Pant D, Zheng H, Maas NL, et al. miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell 2012;48:353-64.   DOI
94 Liu Y, Liu T, Lei T, Zhang D, Du S, Girani L, et al. RIP1/RIP3-regulated necroptosis as a target for multifaceted disease therapy (Review). Int J Mol Med 2019;44:771-86.
95 MacEwan DJ. TNF ligands and receptors: a matter of life and death. Br J Pharmacol 2002;135:855-75.   DOI
96 Wang K, Liu F, Zhou LY, Ding SL, Long B, Liu CY, et al. miR874 regulates myocardial necrosis by targeting caspase-8. Cell Death Dis 2013;4:e709.   DOI
97 Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435:834-8.   DOI
98 Andalib A, Rashed S, Dehbashi M, Hajati J, Noorbakhsh F, Ganjalikhani-Hakemi M. The upregulation of hsa-mir-181b-1 and downregulation of its target CYLD in the late-stage of tumor progression of breast cancer. Indian J Clin Biochem 2020;35:312-21.   DOI
99 Grammatikakis I, Gorospe M, Abdelmohsen K. Modulation of cancer traits by tumor suppressor microRNAs. Int J Mol Sci 2013;14:1822-42.   DOI
100 Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol 2014;9:287-314.   DOI