Regulation of autophagy by miRNAs in human diseases
Tóm tắt
Autophagy is a homeostatic process designed to eliminate dysfunctional and aging organelles and misfolded proteins through a well-concerted pathway, starting with forming a double-membrane vesicle and culminating in the lysosomal degradation of the cargo enclosed inside the mature vesicle. As a vital sentry of cellular health, autophagy is regulated in every human disease condition and is an essential target for non-coding RNAs like microRNAs (miRNAs). miRNAs are short oligonucleotides that specifically bind to the 3'-untranslated region (UTR) of target mRNAs, thus leading to mRNA silencing, degradation, or translation blockage. This review summarizes the recent findings regarding the regulation of autophagy and autophagy-related genes by different miRNAs in various pathological conditions, including cancer, kidney and liver disorders, neurodegeneration, cardiovascular disorders, infectious diseases, aging-related conditions, and inflammation-related diseases. As miRNAs are being identified as prime regulators of autophagy in human disease, pharmacological molecules and traditional medicines targeting these miRNAs are also being tested in disease models, thus initiating a new series of therapeutic interventions targeting autophagy.
Tài liệu tham khảo
Abdellatif M, Ljubojevic-Holzer S, Madeo F, Sedej S. Autophagy in cardiovascular health and disease. Prog Mol Biol Transl Sci. 2020;172:87–106.
Akkoc Y, Gozuacik D. MicroRNAs as major regulators of the autophagy pathway. Biochim Biophys Acta Mol Cell Res. 2020;1867:118662.
Atala A. Re: VHL-Regulated miR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. J Urol. 2012;188:2434.
Balzano F, Campesi I, Cruciani S, Garroni G, Bellu E, et al. Epigenetics, stem cells, and autophagy: exploring a path involving miRNA. Int J Mol Sci. 2019;20:5091.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
Bhatia D, Choi ME. Autophagy in kidney disease: advances and therapeutic potential. Prog Mol Biol Transl Sci. 2020;172:107–33.
Buque Martinez A, Galluzzi L. Preface-Autophagy: An old mechanism with new challenges ahead. Prog Mol Biol Transl Sci. 2020;172:xv–xix.
Chang Y, Yan W, He X, Zhang L, Li C, et al. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology. 2012;143:177–87.
Chen D, Huang X, Lu S, Deng H, Gan H, et al. miRNA-125a modulates autophagy of thyroiditis through PI3K/Akt/mTOR signaling pathway. Exp Ther Med. 2019;17:2465–72.
Chen DY, Chen YM, Lin CF, Lo CM, Liu HJ, Liao TL. MicroRNA-889 inhibits autophagy to maintain mycobacterial survival in patients with latent tuberculosis infection by targeting TWEAK. mBio. 2020;11:e03045.
Chen J, Cui Y, Zhang N, Yao X, Wang Z, Yang L. Oleanolic acid attenuated diabetic mesangial cell injury by activation of autophagy via miRNA-142-5p/PTEN signaling. Cytotechnology. 2019;71:925–33.
Chen J, Sun Q, Liu GZ, Zhang F, Liu CY, et al. Effect of miR-202-5p-mediated ATG7 on autophagy and apoptosis of degenerative nucleus pulposus cells. Eur Rev Med Pharmacol Sci. 2020;24:517–25.
Chen L, Ming X, Li W, Bi M, Yan B, et al. The microRNA-155 mediates hepatitis B virus replication by reinforcing SOCS1 signalling-induced autophagy. Cell Biochem Funct. 2020;38:436–42.
Chen W, Li Z, Liu H, Jiang S, Wang G, et al. MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib. Cell Death Dis. 2020;11:198.
Cheng Y, Li Z, Xie J, Wang P, Zhu J, et al. MiRNA-224-5p inhibits autophagy in breast cancer cells via targeting Smad4. Biochem Biophys Res Commun. 2018;506:793–8.
Comincini S, Allavena G, Palumbo S, Morini M, Durando F, et al. microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. Cancer Biol Ther. 2013;14:574–86.
D’Adamo S, Cetrullo S, Minguzzi M, Silvestri Y, Borzi RM, Flamigni F. MicroRNAs and autophagy: fine players in the control of chondrocyte homeostatic activities in osteoarthritis. Oxid Med Cell Longev. 2017;2017:3720128.
Deretic V, Klionsky DJ. Autophagy and inflammation: a special review issue. Autophagy. 2018;14:179–80.
Deshpande S, Abdollahi M, Wang M, Lanting L, Kato M, Natarajan R. Reduced autophagy by a microRNA-mediated signaling cascade in diabetes-induced renal glomerular hypertrophy. Sci Rep. 2018;8:6954.
Dinesh Kumar N, Smit JM, Reggiori F. Strategies employed by viruses to manipulate autophagy. Prog Mol Biol Transl Sci. 2020;172:203–37.
Engedal N, Zerovnik E, Rudov A, Galli F, Olivieri F, et al. From oxidative stress damage to pathways, networks, and autophagy via MicroRNAs. Oxid Med Cell Longev. 2018;2018:4968321.
Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74.
Feng L, Feng C, Wang CX, Xu DY, Chen JJ, et al. Circulating microRNA let7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy. Int J Mol Med. 2020;45:1464–76.
Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102–14.
Frankel LB, Lund AH. MicroRNA regulation of autophagy. Carcinogenesis. 2012;33:2018–25.
He W, Ni W, Zhao L, Wang X, Liu L, Fan Z. MicroRNA-125a/VDR axis impaired autophagic flux and contributed to fibrosis in a CCL4-induced mouse model and patients with liver cirrhosis. Life Sci. 2021;264:118666.
Holla S, Kurowska-Stolarska M, Bayry J, Balaji KN. Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling. Autophagy. 2014;10:311–30.
Huang K, Sun X, Wu H, Zhao J, Jian Y, et al. The regulating effect of autophagy-related MiRNAs in kidney, bladder, and prostate cancer. J Oncol. 2021;2021:5510318.
Jiang PC, Bu SR. Clinical value of circular RNAs and autophagy-related miRNAs in the diagnosis and treatment of pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2019;18:511–6.
Kim JK, Kim TS, Basu J, Jo EK. MicroRNA in innate immunity and autophagy during mycobacterial infection. Cell Microbiol. 2017;19:e12687.
Kim JK, Lee HM, Park KS, Shin DM, Kim TS, et al. MIR144* inhibits antimicrobial responses against Mycobacterium tuberculosis in human monocytes and macrophages by targeting the autophagy protein DRAM2. Autophagy. 2017;13:423–41.
Kim JK, Yuk JM, Kim SY, Kim TS, Jin HS, et al. MicroRNA-125a inhibits autophagy activation and antimicrobial responses during mycobacterial infection. J Immunol. 2015;194:5355–65.
Kou X, Chen N. Resveratrol as a natural autophagy regulator for prevention and treatment of Alzheimer’s disease. Nutrients. 2017;9:927.
Kumar R, Sahu SK, Kumar M, Jana K, Gupta P, et al. MicroRNA 17–5p regulates autophagy in Mycobacterium tuberculosis-infected macrophages by targeting Mcl-1 and STAT3. Cell Microbiol. 2016;18:679–91.
Lai L, Chen J, Wang N, Zhu G, Duan X, Ling F. MiRNA-30e mediated cardioprotection of ACE2 in rats with Doxorubicin-induced heart failure through inhibiting cardiomyocytes autophagy. Life Sci. 2017;169:69–75.
Lan T, Shiyu H, Shen Z, Yan B, Chen J. New insights into the interplay between miRNAs and autophagy in the aging of intervertebral discs. Ageing Res Rev. 2021;65:101227.
Larabi A, Dalmasso G, Delmas J, Barnich N, Nguyen HTT. Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn’s disease-associated adherent-invasive E. coli. Gut Microbes. 2020;11:1677–94.
Li BB, Chen YL, Pang F. MicroRNA-30a targets ATG5 and attenuates airway fibrosis in asthma by suppressing autophagy. Inflammation. 2020;43:44–53.
Li C, Yang L, Wu H, Dai M. Paeonol inhibits oxidized low-density lipoprotein-induced vascular endothelial cells autophagy by upregulating the expression of miRNA-30a. Front Pharmacol. 2018;9:95.
Li H, Li Z, Pi Y, Chen Y, Mei L, et al. MicroRNA-375 exacerbates knee osteoarthritis through repressing chondrocyte autophagy by targeting ATG2B. Aging (Albany NY). 2020;12:7248–61.
Li Q, Wang Y, Peng W, Jia Y, Tang J, et al. MicroRNA-101a regulates autophagy phenomenon via the MAPK pathway to modulate Alzheimer’s-associated pathogenesis. Cell Transplant. 2019;28:1076–84.
Liao W, Zhang Y. MicroRNA-381 facilitates autophagy and apoptosis in prostate cancer cells via inhibiting the RELN-mediated PI3K/AKT/mTOR signaling pathway. Life Sci. 2020;254:117672.
Lin H, Zhang W, Zhou T, Li W, Chen Z, et al. Mechanism of microRNA-21 regulating IL-6 inflammatory response and cell autophagy in intervertebral disc degeneration. Exp Ther Med. 2017;14:1441–4.
Liu G, Kang X, Guo P, Shang Y, Du R, et al. miR-25-3p promotes proliferation and inhibits autophagy of renal cells in polycystic kidney mice by regulating ATG14-Beclin 1. Ren Fail. 2020;42:333–42.
Liu KX, Chen GP, Lin PL, Huang JC, Lin X, et al. Detection and analysis of apoptosis- and autophagy-related miRNAs of mouse vascular endothelial cells in chronic intermittent hypoxia model. Life Sci. 2018;193:194–9.
Liu X, Zhong L, Li P, Zhao P. 2020. MicroRNA-100 Enhances autophagy and suppresses migration and invasion of renal cell carcinoma cells via disruption of NOX4-dependent mTOR Pathway. Clin Transl Sci.
Lu X, Fan Q, Xu L, Li L, Yue Y, et al. Ursolic acid attenuates diabetic mesangial cell injury through the up-regulation of autophagy via miRNA-21/PTEN/Akt/mTOR suppression. PLoS One. 2015;10:e0117400.
Luo P, Gao F, Niu D, Sun X, Song Q, et al. The role of autophagy in chondrocyte metabolism and osteoarthritis: a comprehensive research review. Biomed Res Int. 2019;2019:5171602.
Lv Q, Zhong Z, Hu B, Yan S, Yan Y, et al. MicroRNA-3473b regulates the expression of TREM2/ULK1 and inhibits autophagy in inflammatory pathogenesis of Parkinson disease. J Neurochem. 2021;157:599–610.
Ma J, Wang Y, Xu HT, Ren N, Zhao N, et al. MicroRNA: a novel biomarker and therapeutic target to combat autophagy in diabetic nephropathy. Eur Rev Med Pharmacol Sci. 2019;23:6257–63.
Ma Z, Li L, Livingston MJ, Zhang D, Mi Q, et al. p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. J Clin Invest. 2020;130:5011–26.
Meng CY, Zhao ZQ, Bai R, Zhao W, Wang YX, et al. MicroRNA22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Oncol Rep. 2020;43:1169–86.
Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, 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.
Mukhopadhyay U, Chanda S, Patra U, Mukherjee A, Rana S, et al. Synchronized orchestration of miR-99b and let-7g positively regulates rotavirus infection by modulating autophagy. Sci Rep. 2019;9:1318.
Munz C. Autophagy in immunity. Prog Mol Biol Transl Sci. 2020;172:67–85.
Nehammer C, Ejlerskov P, Gopal S, Handley A, Ng L, et al. Interferon-beta-induced miR-1 alleviates toxic protein accumulation by controlling autophagy. Elife. 2019;8:e49930.
Patergnani S, Guzzo S, Mangolini A, dell’Atti L, Pinton P, Aguiari G. The induction of AMPK-dependent autophagy leads to P53 degradation and affects cell growth and migration in kidney cancer cells. Exp Cell Res. 2020;395:112190.
Peng N, He J, Li J, Huang H, Huang W, et al. Long noncoding RNA MALAT1 inhibits the apoptosis and autophagy of hepatocellular carcinoma cell by targeting the microRNA-146a/PI3K/Akt/mTOR axis. Cancer Cell Int. 2020;20:165.
Pulakat L, Chen HH. Pro-senescence and anti-senescence mechanisms of cardiovascular aging: cardiac MicroRNA regulation of longevity drug-induced autophagy. Front Pharmacol. 2020;11:774.
Qiao PF, Yao L, Zeng ZL. Catalpolmediated microRNA34a suppresses autophagy and malignancy by regulating SIRT1 in colorectal cancer. Oncol Rep. 2020;43:1053–66.
Racanelli AC, Choi AMK, Choi ME. Autophagy in chronic lung disease. Prog Mol Biol Transl Sci. 2020;172:135–56.
Ren Y, Chen Y, Liang X, Lu Y, Pan W, Yang M. MiRNA-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3. Cancer Lett. 2017;390:126–36.
Rodriguez-Muela N. Autophagy in motor neuron diseases. Prog Mol Biol Transl Sci. 2020;172:157–202.
Saha S, Panigrahi DP, Patil S, Bhutia SK. Autophagy in health and disease: a comprehensive review. Biomed Pharmacother. 2018;104:485–95.
Santovito D, Egea V, Bidzhekov K, Natarelli L, Mourao A, et al. Noncanonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis. Sci Transl Med. 2020;12:eaaz294.
Shang J, Chen ZZ, Wang ZH, Wei TN, Wu WB, Chen WM. Association of miRNA-196b-5p and miRNA-99a-5p with autophagy and apoptosis in multiple myeloma cells. Zhonghua Xue Ye Xue Za Zhi. 2018;39:766–72.
Shang Y, Liu Q, Wang L, Qiu X, Chen Y, An J. microRNA-146a-5p negatively modulates PM2.5 caused inflammation in THP-1 cells via autophagy process. Environ Pollut. 2021;268:115961.
Shao G, Zhao Z, Zhao W, Hu G, Zhang L, et al. Long non-coding RNA MALAT1 activates autophagy and promotes cell proliferation by downregulating microRNA-204 expression in gastric cancer. Oncol Lett. 2020;19:805–12.
Shi Q, Jin X, Fan R, Xing M, Guo J, et al. Cadmium-mediated miR-30a-GRP78 leads to JNK-dependent autophagy in chicken kidney. Chemosphere. 2019;215:710–5.
Silwal P, Kim YS, Basu J, Jo EK. The roles of microRNAs in regulation of autophagy during bacterial infection. Semin Cell Dev Biol. 2020;101:51–8.
Stiuso P, Potenza N, Lombardi A, Ferrandino I, Monaco A, et al. MicroRNA-423–5p promotes autophagy in cancer cells and is increased in serum from hepatocarcinoma patients treated with sorafenib. Mol Ther Nucleic Acids. 2015;4:e233.
Sun T, Li MY, Li PF, Cao JM. MicroRNAs in cardiac autophagy: small molecules and big role. Cells. 2018;7:104.
Sun W, Li Y, Wei S. miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis. Exp Ther Med. 2018;15:1119–28.
Szekerczes T, Gogl A, Illyes I, Mandl J, Borka K, et al. Autophagy, mitophagy and microrna expression in chronic hepatitis C and autoimmune hepatitis. Pathol Oncol Res. 2020;26:2143–51.
Wang C, Yang W, Liang X, Song W, Lin J, et al. MicroRNA-761 modulates foam cell formation and inflammation through autophagy in the progression of atherosclerosis. Mol Cell Biochem. 2020;474:135–46.
Wang C, Zhang ZZ, Yang W, Ouyang ZH, Xue JB, et al. MiR-210 facilitates ECM degradation by suppressing autophagy via silencing of ATG7 in human degenerated NP cells. Biomed Pharmacother. 2017;93:470–9.
Wang IK, Sun KT, Tsai TH, Chen CW, Chang SS, et al. MiR-20a-5p mediates hypoxia-induced autophagy by targeting ATG16L1 in ischemic kidney injury. Life Sci. 2015;136:133–41.
Wang P, Zhang J, Zhang L, Zhu Z, Fan J, et al. MicroRNA 23b regulates autophagy associated with radioresistance of pancreatic cancer cells. Gastroenterology. 2013;145:1133–43.
Wang S, Guo D, Li C. Downregulation of miRNA-26b inhibits cancer proliferation of laryngeal carcinoma through autophagy by targeting ULK2 and inactivation of the PTEN/AKT pathway. Oncol Rep. 2017;38:1679–87.
Wang WJ, Yang W, Ouyang ZH, Xue JB, Li XL, et al. MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells. Biomed Pharmacother. 2018;99:725–34.
Wang XB, Wang H, Long HQ, Li DY, Zheng X. LINC00641 regulates autophagy and intervertebral disc degeneration by acting as a competitive endogenous RNA of miR-153-3p under nutrition deprivation stress. J Cell Physiol. 2019;234:7115–27.
Wang Z, Hu J, Pan Y, Shan Y, Jiang L, et al. miR-140-5p/miR-149 affects chondrocyte proliferation, apoptosis, and autophagy by targeting FUT1 in osteoarthritis. Inflammation. 2018;41:959–71.
Wang Z, Hu J, Pan Y, Shan Y, Jiang L, et al. Correction to: miR-140-5p/miR-149 affects chondrocyte proliferation, apoptosis, and autophagy by targeting FUT1 in osteoarthritis. Inflammation. 2019;42:1515–6.
Wang Z, Yuan B, Fu F, Huang S, Yang Z. Hemoglobin enhances miRNA-144 expression and autophagic activation mediated inflammation of microglia via mTOR pathway. Sci Rep. 2017;7:11861.
Wei DM, Jiang MT, Lin P, Yang H, Dang YW, et al. Potential ceRNA networks involved in autophagy suppression of pancreatic cancer caused by chloroquine diphosphate: a study based on differentiallyexpressed circRNAs, lncRNAs, miRNAs and mRNAs. Int J Oncol. 2019;54:600–26.
Wei L, Chen Z, Cheng N, Li X, Chen J, et al. MicroRNA-126 inhibit viability of colorectal cancer cell by repressing mTOR induced apoptosis and autophagy. Onco Targets Ther. 2020;13:2459–68.
Xiang J, Jiang T, Zhang W, Xie W, Tang X, Zhang J. Human umbilical cord-derived mesenchymal stem cells enhanced HK-2 cell autophagy through MicroRNA-145 by inhibiting the PI3K/AKT/mTOR signaling pathway. Exp Cell Res. 2019;378:198–205.
Xu XH, Ding DF, Yong HJ, Dong CL, You N, et al. Resveratrol transcriptionally regulates miRNA-18a-5p expression ameliorating diabetic nephropathy via increasing autophagy. Eur Rev Med Pharmacol Sci. 2017;21:4952–65.
Yan L, Guo N, Cao Y, Zeng S, Wang J, et al. miRNA145 inhibits myocardial infarctioninduced apoptosis through autophagy via Akt3/mTOR signaling pathway in vitro and in vivo. Int J Mol Med. 2018;42:1537–47.
Yang S, Abdulla R, Lu C, Zhang L. Inhibition of microRNA-376b protects against renal interstitial fibrosis via inducing macrophage autophagy by upregulating Atg5 in mice with chronic kidney disease. Kidney Blood Press Res. 2018;43:1749–64.
Yang S, Wang M, Yang L, Li Y, Ma Y, et al. MicroRNA-375 targets ATG14 to inhibit autophagy and sensitize hepatocellular carcinoma cells to sorafenib. Onco Targets Ther. 2020;13:3557–70.
Yang Y, Sun Y, Wang H, Li H, Zhang M, et al. MicroRNA-221 induces autophagy through suppressing HDAC6 expression and promoting apoptosis in pancreatic cancer. Oncol Lett. 2018;16:7295–301.
Yu A, Zhang T, Zhong W, Duan H, Wang S, et al. miRNA-144 induces microglial autophagy and inflammation following intracerebral hemorrhage. Immunol Lett. 2017;182:18–23.
Yu Y, Zhao J. Modulated autophagy by MicroRNAs in osteoarthritis chondrocytes. Biomed Res Int. 2019;2019:1484152.
Yun Z, Wang Y, Feng W, Zang J, Zhang D, Gao Y. Overexpression of microRNA-185 alleviates intervertebral disc degeneration through inactivation of the Wnt/beta-catenin signaling pathway and downregulation of Galectin-3. Mol Pain. 2020;16:1744806920902559.
Zhang H, Liang H, Wu S, Zhang Y, Yu Z. MicroRNA-638 induces apoptosis and autophagy in human liver cancer cells by targeting enhancer of zeste homolog 2 (EZH2). Environ Toxicol Pharmacol. 2021;82:103559.
Zhang W, Dong YZ, Du X, Peng XN, Shen QM. MiRNA-153-3p promotes gefitinib-sensitivity in non-small cell lung cancer by inhibiting ATG5 expression and autophagy. Eur Rev Med Pharmacol Sci. 2019;23:2444–52.
Zhang W, Liu Y, Fu Y, Han W, Xu H, et al. Long non-coding RNA LINC00160 functions as a decoy of microRNA-132 to mediate autophagy and drug resistance in hepatocellular carcinoma via inhibition of PIK3R3. Cancer Lett. 2020;478:22–33.
Zhang X, Yang K, Le W. Autophagy and motor neuron diseases. Adv Exp Med Biol. 2020;1207:53–74.
Zhang Y, Zhao S, Wu D, Liu X, Shi M, et al. MicroRNA-22 promotes renal tubulointerstitial fibrosis by targeting PTEN and suppressing autophagy in diabetic nephropathy. J Diabetes Res. 2018;2018:4728645.
Zhao K, Zhang Y, Kang L, Song Y, Wang K, et al. Methylation of microRNA-129-5P modulates nucleus pulposus cell autophagy by targeting Beclin-1 in intervertebral disc degeneration. Oncotarget. 2017;8:86264–76.
Zhong G, Long H, Ma S, Shunhan Y, Li J, Yao J. miRNA-335-5p relieves chondrocyte inflammation by activating autophagy in osteoarthritis. Life Sci. 2019;226:164–72.
Zhou Y, Wang X, Song M, He Z, Cui G, et al. A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing. Nat Commun. 2019;10:4827.
Zhu H, Wu H, Liu X, Li B, Chen Y, et al. Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy. 2009;5:816–23.