CLC number: R737.9
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2020-07-10
Cited: 0
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Nan Wen, Qing Lv, Zheng-Gui Du. MicroRNAs involved in drug resistance of breast cancer by regulating autophagy[J]. Journal of Zhejiang University Science B, 2020, 21(9): 690-702.
@article{title="MicroRNAs involved in drug resistance of breast cancer by regulating autophagy",
author="Nan Wen, Qing Lv, Zheng-Gui Du",
journal="Journal of Zhejiang University Science B",
volume="21",
number="9",
pages="690-702",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000076"
}
%0 Journal Article
%T MicroRNAs involved in drug resistance of breast cancer by regulating autophagy
%A Nan Wen
%A Qing Lv
%A Zheng-Gui Du
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 9
%P 690-702
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000076
TY - JOUR
T1 - MicroRNAs involved in drug resistance of breast cancer by regulating autophagy
A1 - Nan Wen
A1 - Qing Lv
A1 - Zheng-Gui Du
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 9
SP - 690
EP - 702
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000076
Abstract: autophagy is a conserved catabolic process characterized by degradation and recycling of cytosolic components or organelles through a lysosome-dependent pathway. It has a complex and close relationship to drug resistance in breast cancer. microRNAs (miRNAs) are small noncoding molecules that can influence numerous cellular processes including autophagy, through the posttranscriptional regulation of gene expression. autophagy is regulated by many proteins and pathways, some of which in turn have been found to be regulated by miRNAs. These miRNAs may affect the drug resistance of breast cancer. drug resistance is the main cause of distant recurrence, metastasis and death in breast cancer patients. In this review, we summarize the causative relationship between autophagy and drug resistance of breast cancer. The roles of autophagy-related proteins and pathways and their associated miRNAs in drug resistance of breast cancer are also discussed.
[1]Abdel-Mohsen MA, Abdel Malak CA, El-Shafey ES, 2019. Influence of copper (I) nicotinate complex and autophagy modulation on doxorubicin-induced cytotoxicity in HCC1806 breast cancer cells. Adv Med Sci, 64(1):202-209.
[2]Ahmad A, Zhang WJ, Wu MM, et al., 2018. Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes. Genes Genomics, 40(3):243-251.
[3]Alers S, Löffler AS, Wesselborg S, et al., 2012. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol, 32(1):2-11.
[4]Bamodu OA, Kuo KT, Yuan LP, et al., 2018. HDAC inhibitor suppresses proliferation and tumorigenicity of drug-resistant chronic myeloid leukemia stem cells through regulation of hsa-miR-196a targeting BCR/ABL1. Exp Cell Res, 370(2):519-530.
[5]Bartel DP, 2009. MicroRNAs: target recognition and regulatory functions. Cell, 136(2):215-233.
[6]Bialik S, Dasari SK, Kimchi A, 2018. Autophagy-dependent cell death—where, how and why a cell eats itself to death. J Cell Sci, 131(18):jcs215152.
[7]Bian XH, Liang ZX, Feng A, et al., 2018. HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL. Biochem Pharmacol, 147:30-37.
[8]Bockhorn J, Dalton R, Nwachukwu C, et al., 2013. MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat Commun, 4:1393.
[9]Bolden JE, Peart MJ, Johnstone RW, 2006. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov, 5(9):769-784.
[10]Button RW, Roberts SL, Willis TL, et al., 2017. Accumulation of autophagosomes confers cytotoxicity. J Biol Chem, 292(33):13599-13614.
[11]Chan JK, Kiet TK, Blansit K, et al., 2014. MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecol Oncol, 133(3):568-574.
[12]Chen LQ, Bourguignon LYW, 2014. Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer, 13:52.
[13]Cheng X, Tan SR, Duan FF, et al., 2019. Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM. Breast Cancer, 26(6):766-775.
[14]Cittelly DM, Das PM, Spoelstra NS, et al., 2010. Downregulation of miR-342 is associated with tamoxifen resistant breast tumors. Mol Cancer, 9:317.
[15]Clarke R, Tyson JJ, Dixon JM, 2015. Endocrine resistance in breast cancer—an overview and update. Mol Cell Endocrinol, 418:220-234.
[16]Dai XF, Li T, Bai ZH, et al., 2015. Breast cancer intrinsic subtype classification, clinical use and future trends. Am J Cancer Res, 5(10):2929-2943.
[17]Decressac M, Mattsson B, Weikop P, et al., 2013. TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity. Proc Natl Acad Sci USA, 110(19):E1817-E1826.
[18]Dong HY, Hu JG, Zou KJ, et al., 2019. Activation of lncRNA TINCR by H3K27 acetylation promotes trastuzumab resistance and epithelial-mesenchymal transition by targeting microRNA-125b in breast cancer. Mol Cancer, 18(1):3.
[19]Dong XL, Yang Y, Zhou Y, et al., 2019. Glutathione S-transferases P1 protects breast cancer cell from adriamycin-induced cell death through promoting autophagy. Cell Death Differ, 26(10):2086-2099.
[20]Fahad Ullah M, 2019. Breast cancer: current perspectives on the disease status. In: Ahmad A (Ed.), Breast Cancer Metastasis and Drug Resistance. Springer, Cham, p.51-64.
[21]Fan WX, Wen XL, Xiao H, et al., 2018. MicroRNA-29a enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis by targeting heme oxygenase-1. Eur Rev Med Pharmacol Sci, 22(24):8909-8917.
[22]https://doi.org/10.26355/eurrev_201812_16660
[23]Galluzzi L, Vitale I, Aaronson SA, et al., 2018. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ, 25(3):486-541.
[24]Gonzalez-Malerva L, Park J, Zou LH, et al., 2011. High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci USA, 108(5):2058-2063.
[25]Gou LS, Zhao L, Song WC, et al., 2018. Inhibition of miR-92a suppresses oxidative stress and improves endothelial function by upregulating heme oxygenase-1 in db/db mice. Antioxid Redox Signal, 28(5):358-370.
[26]Green DR, Llambi F, 2015. Cell death signaling. Cold Spring Harb Perspect Biol, 7(12):a006080.
[27]Gu Y, Chen TX, Li GL, et al., 2017. Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer. Oncotarget, 8(32):52156-52177.
[28]https://doi.org/10.18632/oncotarget.11044
[29]Guestini F, Mcnamara KM, Ishida T, et al., 2016. Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification. Expert Opin Ther Targets, 20(6):705-720.
[30]Guo JY, Chen HY, Mathew R, et al., 2011. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev, 25(5):460-470.
[31]Hanahan D, Weinberg RA, 2011. Hallmarks of cancer: the next generation. Cell, 144(5):646-674.
[32]He X, Xiao X, Dong L, et al., 2015. miR-218 regulates cisplatin chemosensitivity in breast cancer by targeting BRCA1. Tumour Biol, 36(3):2065-2075.
[33]Heng MY, Detloff PJ, Paulson HL, et al., 2010. Early alterations of autophagy in huntington disease-like mice. Autophagy, 6(8):1206-1208.
[34]Hosokawa N, Hara T, Kaizuka T, et al., 2009. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell, 20(7):1981-1991.
[35]Hsieh TH, Hsu CY, Tsai CF, et al., 2015. HDAC inhibitors target HDAC5, upregulate microRNA-125a-5p, and induce apoptosis in breast cancer cells. Mol Ther, 23(4):656-666.
[36]Jeon HS, Lee SY, Lee EJ, et al., 2012. Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer. Lung Cancer, 76(2):171-176.
[37]Jung CH, Jun CB, Ro SH, et al., 2009. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell, 20(7):1992-2003.
[38]Jung DE, Park SB, Kim K, et al., 2017. CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway. Sci Rep, 7(1):10921.
[39]Kim HJ, Lee SG, Kim YJ, et al., 2013. Cytoprotective role of autophagy during paclitaxel-induced apoptosis in Saos-2 osteosarcoma cells. Int J Oncol, 42(6):1985-1992.
[40]Kim HS, Tian LJ, Jung M, et al., 2015. Downregulation of choline kinase-alpha enhances autophagy in tamoxifen-resistant breast cancer cells. PLoS ONE, 10(10):e0141110.
[41]Kimura T, Takabatake Y, Takahashi A, et al., 2013. Chloroquine in cancer therapy: a double-edged sword of autophagy. Cancer Res, 73(1):3-7.
[42]Lai TH, Ewald B, Zecevic A, et al., 2016. HDAC inhibition induces microRNA-182, which targets RAD51 and impairs HR repair to sensitize cells to sapacitabine in acute myelogenous leukemia. Clin Cancer Res, 22(14):3537-3549.
[43]Lee YJ, Won AJ, Lee J, et al., 2012. Molecular mechanism of SAHA on regulation of autophagic cell death in tamoxifen-resistant MCF-7 breast cancer cells. Int J Med Sci, 9(10):881-893.
[44]Levine B, Klionsky DJ, 2004. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell, 6(4):463-477.
[45]Li FJ, Miao LX, Xue T, et al., 2019. Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells. J Exp Clin Cancer Res, 38(1):414.
[46]Li W, Zhang LN, 2019. Regulation of ATG and autophagy initiation. In: Qin ZH (Ed.), Autophagy: Biology and Diseases. Springer, Singapore, p.41-65.
[47]Li Y, Zou LH, Li QY, et al., 2010. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med, 16(2):214-218.
[48]Li Y, Zhang Q, Tian RY, et al., 2011. Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res, 71(24):7481-7489.
[49]Li Y, Iglehart JD, Richardson AL, et al., 2012. The amplified cancer gene LAPTM4B promotes tumor growth and tolerance to stress through the induction of autophagy. Autophagy, 8(2):273-274.
[50]Li YJ, Lei YH, Yao N, et al., 2017. Autophagy and multidrug resistance in cancer. Chin J Cancer, 36:52.
[51]Lin C, Xie LY, Lu Y, et al., 2018. miR-133b reverses cisplatin resistance by targeting GSTP1 in cisplatin-resistant lung cancer cells. Int J Mol Med, 41(4):2050-2058.
[52]Liu LM, Shen WF, Zhu ZH, et al., 2018. Combined inhibition of EGFR and c-ABL suppresses the growth of fulvestrant-resistant breast cancer cells through miR-375-autophagy axis. Biochem Biophys Res Commun, 498(3):559-565.
[53]Lu J, Sun DP, Gao S, et al., 2014. Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cells. J Pharmacol Sci, 125(1):74-82.
[54]Lui A, New J, Ogony J, et al., 2016. Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells. BMC Cancer, 16:487.
[55]Ma X, Chen Z, Hua D, et al., 2014. Essential role for trpC5-containing extracellular vesicles in breast cancer with chemotherapeutic resistance. Proc Natl Acad Sci USA, 111(17):6389-6394.
[56]Miller TE, Ghoshal K, Ramaswamy B, et al., 2008. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27kip1. J Biol Chem, 283(44):29897-29903.
[57]Musolino A, Naldi N, Bortesi B, et al., 2008. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/ neu-positive metastatic breast cancer. J Clin Oncol, 26(11):1789-1796.
[58]Napoli M, Venkatanarayan A, Raulji P, et al., 2016. ΔNp63/ DGCR8-dependent microRNAs mediate therapeutic efficacy of HDAC inhibitors in cancer. Cancer Cell, 29(6):874-888.
[59]Noonan EJ, Place RF, Pookot D, et al., 2009. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene, 28(14):1714-1724.
[60]O'Brien K, Lowry MC, Corcoran C, et al., 2015. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity. Oncotarget, 6(32):32774-32789.
[61]https://doi.org/10.18632/oncotarget.5192
[62]Pan BZ, Yi J, Song HZ, 2013. MicroRNA-mediated autophagic signaling networks and cancer chemoresistance. Cancer Biother Radiopharm, 28(8):573-578.
[63]Park JH, Ahn MY, Kim TH, et al., 2012. A new synthetic HDAC inhibitor, MHY218, induces apoptosis or autophagy-related cell death in tamoxifen-resistant MCF-7 breast cancer cells. Invest New Drugs, 30(5):1887-1898.
[64]Park JH, Kim KP, Ko JJ, et al., 2016. PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy. Biochem Biophys Res Commun, 477(2):277-282.
[65]Pei L, Kong YR, Shao CF, et al., 2018. Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to pharmorubicin by promoting autophagy via PI3K/Akt pathway. J Cell Mol Med, 22(11):5311-5321.
[66]Periyasamy-Thandavan S, Jackson WH, Samaddar JS, et al., 2010. Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress, and induces caspase-dependent cell death in antiestrogen-sensitive and resistant ER+ breast cancer cells. Autophagy, 6(1):19-35.
[67]Pu MF, Li CG, Qi XM, et al., 2017. miR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth. PLoS Genet, 13(7):e1006896.
[68]Qadir MA, Kwok B, Dragowska WH, et al., 2008. Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Res Treat, 112(3):389-403.
[69]Rabinowitz JD, White E, 2010. Autophagy and metabolism. Science, 330(6009):1344-1348.
[70]Robertson ED, Wasylyk C, Ye T, et al., 2014. The oncogenic microRNA hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response. PLoS ONE, 9(11):e113050.
[71]Romero MA, Bayraktar Ekmekcigil O, Bagca BG, et al., 2019. Role of autophagy in breast cancer development and progression: opposite sides of the same coin. In: Ahmad A (Ed.), Breast Cancer Metastasis and Drug Resistance. Springer, Cham, p.65-73.
[72]Ru P, Steele R, Hsueh EC, et al., 2011. Anti-miR-203 upregulates SOCS3 expression in breast cancer cells and enhances cisplatin chemosensitivity. Genes Cancer, 2(7):720-727.
[73]Schwartz-Roberts JL, Shajahan AN, Cook KL, et al., 2013. GX15-070 (obatoclax) induces apoptosis and inhibits cathepsin
[74]Shen HM, Codogno P, 2011. Autophagic cell death: Loch Ness monster or endangered species? Autophagy, 7(5):457-465.
[75]Shi SJ, Wang LJ, Yu B, et al., 2015. LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer. Oncotarget, 6(13):11652-11663.
[76]https://doi.org/10.18632/oncotarget.3457
[77]Shi Y, Gong WH, Lu L, et al., 2019. Upregulation of miR-129-5p increases the sensitivity to taxol through inhibiting HMGB1-mediated cell autophagy in breast cancer MCF-7 cells. Braz J Med Biol Res, 52(11):e8657.
[78]Soni M, Patel Y, Markoutsa E, et al., 2018. Autophagy, cell viability, and chemoresistance are regulated by miR-489 in breast cancer. Mol Cancer Res, 16(9):1348-1360.
[79]Sun DJ, Zhu LJ, Zhao YQ, et al., 2018. Fluoxetine induces autophagic cell death via eEF2K-AMPK-mTOR-ULK complex axis in triple negative breast cancer. Cell Prolif, 51(2):e12402.
[80]Sun WL, Chen J, Wang YP, et al., 2011. Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development. Autophagy, 7(9):1035-1044.
[81]Sun WL, Wang L, Luo J, et al., 2018. Ambra1 modulates the sensitivity of breast cancer cells to epirubicin by regulating autophagy via ATG12. Cancer Sci, 109(10):3129-3138.
[82]Tan X, Peng J, Fu Y, et al., 2014. miR-638 mediated regulation of BRCA1 affects DNA repair and sensitivity to UV and cisplatin in triple-negative breast cancer. Breast Cancer Res, 16:435.
[83]Thomas S, Thurn KT, Biçaku E, et al., 2011. Addition of a histone deacetylase inhibitor redirects tamoxifen-treated breast cancer cells into apoptosis, which is opposed by the induction of autophagy. Breast Cancer Res Treat, 130(2):437-447.
[84]Trüe O, Matthias P, 2012. Interplay between histone deacetylases and autophagy—from cancer therapy to neurodegeneration. Immunol Cell Biol, 90(1):78-84.
[85]Ujihira T, Ikeda K, Suzuki T, et al., 2015. MicroRNA-574-3p, identified by microRNA library-based functional screening, modulates tamoxifen response in breast cancer. Sci Rep, 5:7641.
[86]Vazquez-Martin A, Oliveras-Ferraros C, Menendez JA, 2009. Autophagy facilitates the development of breast cancer resistance to the Anti-HER2 monoclonal antibody trastuzumab. PLoS ONE, 4(7):e6251.
[87]Wang ZY, Wang N, Liu PX, et al., 2014. MicroRNA-25 regulates chemoresistance-associated autophagy in breast cancer cells, a process modulated by the natural autophagy inducer isoliquiritigenin. Oncotarget, 5(16):7013-7026.
[88]https://doi.org/10.18632/oncotarget.2192
[89]Wen X, Klionsky DJ, 2016. An overview of macroautophagy in yeast. J Mol Biol, 428(9):1681-1699.
[90]Wu MY, Fu JJ, Xu JM, et al., 2012. Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor. Cell Res, 22(6):1003-1021.
[91]Xu HD, Qin ZH, 2019. Beclin 1, Bcl-2 and autophagy. In: Qin ZH (Ed.), Autophagy: Biology and Diseases. Springer, Singapore, p.109-126.
[92]Yan XJ, Zhou RM, Ma ZY, 2019. Autophagy—cell survival and death. In: Qin ZH (Ed.), Autophagy: Biology and Diseases. Springer, Singapore, p.667-696.
[93]Yang ZF, Klionsky DJ, 2010. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol, 22(2):124-131.
[94]Yao YS, Qiu WS, Yao RY, et al., 2015. miR-141 confers docetaxel chemoresistance of breast cancer cells via regulation of EIF4E expression. Oncol Rep, 33(5):2504-2512.
[95]Yu XF, Luo AP, Liu YC, et al., 2015. miR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy. Mol Cancer, 14:208.
[96]Yu XF, Li RL, Shi WN, et al., 2016. Silencing of microRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells. Biomed Pharmacother, 77:37-44.
[97]Zhang FF, Wang BB, Long HL, et al., 2016. Decreased miR-124-3p expression prompted breast cancer cell progression mainly by targeting Beclin-1. Clin Lab, 62(6):1139-1145.
[98]Zhang HW, Hu JJ, Fu RQ, et al., 2018. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/ p70s6K/ULK signaling pathway in human breast cancer cells. Sci Rep, 8:11255.
[99]Zhang P, Liu XY, Li HJ, et al., 2017. TRPC5-induced autophagy promotes drug resistance in breast carcinoma via CaMKKβ/AMPKα/mTOR pathway. Sci Rep, 7(1):3158.
[100]Zhang T, Xiang L, 2019. Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/ heme oxygenase-1 signaling pathway. Cell Mol Biol Lett, 24:15.
[101]Zhang XL, Zhu J, Xing RY, et al., 2012. miR-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting GSTP1. Lung Cancer, 77(3):488-494.
[102]Zhong JT, Yu J, Wang HJ, et al., 2017. Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway. Tumour Biol, 39(5):1010428317697562.
[103]Zhou H, Chen Y, Huang SW, et al., 2018. Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(5):333-341.
[104]Zhu HY, Bai WD, Ye XM, et al., 2018. Long non-coding RNA UCA1 desensitizes breast cancer cells to trastuzumab by impeding miR-18a repression of Yes-associated protein 1. Biochem Biophys Res Commun, 496(4):1308-1313.
[105]Zou ZY, Wu LP, Ding HY, et al., 2012. MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing Beclin 1-mediated autophagy. J Biol Chem, 287(6):4148-4156.
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