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miR-183-5p enhances the radioresistance of colorectal cancer by directly targeting ATG5

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Abstract

Radioresistance is a material obstacle for effective treatment of colorectal cancer (CRC). Thus, the discovery of a novel biomarker for determining the CRC radiosensitivity is necessary. Recent studies have confirmed that miR-183-3p regulates cell phenotypes and tumor growth in various cancers. However, the role and mechanism of this micro-ribonucleic acid in CRC radiosensitivity remains unclear. Here, the abundances of miR-183-5p and ATG5 mRNA were detected by a real-time quantitative reverse transcription polymerase chain reaction. Kaplan–Meier survival analysis was carried out to explore the correlation between miR-183-5p and patient prognosis. Cell viability was evaluated by the MTT assay. Survival fraction analysis through colony formation was performed to assess the cell radiation response. Bioinformatic, luciferase and western blot assays were employed to verify the targeted interaction between miR-183-5p and ATG5. The results showed that an elevated abundance of miR-183-5p and a reduced ATG5 level in CRC were associated with the poor prognosis. The knockdown of miR-183-5p enhanced the sensitivity of CRC cells to radiation, inflected by the decreased cell viability and survival fraction. Mechanically, ATG5 was targeted by miR-183-5p. The addition of ATG5 conferred the radiosensitivity of the CRC cells, which was revered by miR-183-5p restoration. Furthermore, miR-183-5p knockdown hindered the tumor growth by repressing ATG5 in vivo after radiation treatment. In summary, the output data indicated that miR-183-5p heightened the radiation response of the CRC cells by targeting ATG5, promising a novel therapeutic target for CRC patients with radioresistance.

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Abbreviations

CRC:

colorectal cancer

3′-UTR:

3′-untranslated regions

FBS:

fetal bovine serum

PVDF:

polyvinylidene difluoride

References

  • An J, Chervin AS, Nie A, Ducoff HS and Huang Z 2007 Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene 26 652–661

    Article  CAS  Google Scholar 

  • Arora H, Qureshi R, Jin S, Park AK and Park WY 2011 miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1. Exp. Mol. Med. 43 298

    Article  CAS  Google Scholar 

  • Banasiak D, Barnetson AR, Odell RA, Mameghan H and Russell PJ 2015 Comparison between the clonogenic, MTT, and SRB assays for determining radiosensitivity in a panel of human bladder cancer cell lines and a ureteral cell line. Radiat. Oncol. Invest. 7 77–85

    Article  Google Scholar 

  • Baerga R, Zhang Y, Chen PH, Goldman S and Jin SV 2009 Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice. Autophagy 5 1118–1130

    Article  CAS  Google Scholar 

  • Bartel D 2009 MicroRNAs: Target recognition and regulatory functions. Cell 136 215–233

    Article  CAS  Google Scholar 

  • Bi DP, Yin CH, Zhang XY, Yang NN and Xu JY 2016 MiR-183 functions as an oncogene by targeting ABCA1 in colon cancer. Oncol. Rep. 35 2873–2879

    Article  CAS  Google Scholar 

  • Cao C, Subhawong T, Albert JM, Kim KW, Geng L, Sekhar KR, Gi YJ and Lu B 2006 Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells. Cancer Res. 66 10040–10047

    Article  CAS  Google Scholar 

  • Cheng Y, Xiang G, Meng Y and Dong R 2016 MiRNA-183-5p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting the PDCD4. Reprod. Biol. 16 225–233

    Article  Google Scholar 

  • Falzone L, Scola L, Zanghì A, Biondi A, Di AC, Libra M and Candido S 2018 Integrated analysis of colorectal cancer microRNA datasets: Identification of microRNAs associated with tumor development. Aging 10 1000–1014

    Article  Google Scholar 

  • Fan H, Yuan R, Cheng S, Xiong K, Zhu X and Zhang Y 2018 Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1. Biomed. Pharmacother. 97 1554–1563

    Article  CAS  Google Scholar 

  • Farniok KE and Levitt SH 2015 The role of radiation therapy in the treatment of colorectal cancer. Cancer 74 2154–9215

    Article  Google Scholar 

  • Gao W, Lin S, Cheng C, Zhu A, Hu Y, Shi Z, Zhang X and Hong Z 2019 Long non-coding RNA CASC2 regulates Sprouty2 via functioning as a competing endogenous RNA for miR-183 to modulate the sensitivity of prostate cancer cells to docetaxel. Arch. Biochem. Biophys. 665 69–78

    Article  CAS  Google Scholar 

  • He RQ, He RQ, Gao L, Gao L, Ma J, Ma J, Li ZY, Li ZY, Hu XH and Hu XH 2018 Oncogenic role of miR-183-5p in lung adenocarcinoma: A comprehensive study of qPCR, in vitro experiments and bioinformatic analysis. Oncol. Rep. 40 83–100

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu JL, He GY, Lan XL, Zeng ZC, Guan J, Ding Y, Qian XL, Liao WT, Ding YQ and Liang L 2018 Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in colorectal cancer. Oncogenesis 7 16

    Article  CAS  Google Scholar 

  • Iorio MV and Croce CM 2013 microRNA involvement in human cancer. Carcinogenesis 59 1126–1133

    Google Scholar 

  • Kim KW, Mutter RW, Cao C, Albert JM, Freeman M, Hallahan DE and Lu B 2006 Autophagy for cancer therapy through inhibition of pro-apoptotic proteins and mammalian target of rapamycin signaling. J. Biol. Chem. 281 36883–36890

    Article  CAS  Google Scholar 

  • Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY and Bapat SA 2009 Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem. Cells 27 10

    Article  Google Scholar 

  • Li F and Sethi G 2010 Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. BBA-Rev. Cancer 1805 167–180

    CAS  Google Scholar 

  • Lin Z, Zhang Y, Liu Y, Zhou M, Lu Y, Li Y, Zhang C, Hong M, Wang S and Li X 2015 MiR-106b induces cell radioresistance via the PTEN/PI3 K/AKT pathways and p21 in colorectal cancer. J. Transl. Med. 13 252

    Article  Google Scholar 

  • Lu YY, Zheng JY, Liu J, Huang CL, Zhang W and Zeng Y 2015 miR-183 induces cell proliferation, migration, and invasion by regulating PDCD4 expression in the SW1990 pancreatic cancer cell line. Biomed. Pharmacother. 70 151–157

    Article  CAS  Google Scholar 

  • Mo N, Lu YK, Xie WM, Liu Y, Zhou WX, Wang HX, Nong L, Jia YX, Tan AH, Chen, Y, Li SS and Luo BH 2014 Inhibition of autophagy enhances the radiosensitivity of nasopharyngeal carcinoma by reducing Rad51 expression. Oncol. Rep. 32 1905–1912

    Article  CAS  Google Scholar 

  • Pedroza-Torres A, López-Urrutia E, García-Castillo V, Jacobo-Herrera N, Herrera LA, Peralta-Zaragoza O, López-Camarillo C, De Leon DC, Fernández-Retana J and Cerna-Cortés JF 2014 MicroRNAs in cervical cancer: Evidences for a miRNA profile deregulated by HPV and its impact on radio-resistance. Molecules 19 6263–6281

    Article  Google Scholar 

  • Sarver AL, Li L and Subramanian S 2010 MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res. 70 9570–9580

    Article  CAS  Google Scholar 

  • Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A and Jemal A 2017 Colorectal cancer statistics, 2017. CA-Cancer J. Clin. 67 104–117

    Google Scholar 

  • Sun Q, Liu T, Yuan Y, Guo Z, Xie G, Du S, Lin X, Xu Z, Liu M and Wang W 2015a MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1. Int. J. Cancer 136 1003–1012

    Article  CAS  Google Scholar 

  • Sun Y, Xing X, Liu Q, Wang Z, Xin Y, Zhang P, Hu C and Liu Y 2015b Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1α/miR-210/Bcl-2 pathway in colon cancer cells. Int. J. Oncol. 46 750–756

    Article  CAS  Google Scholar 

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortettieulent J and Jemal A 2015 Global cancer statistics, 2012. CA Cancer J. Clin. 65 87–108

    Article  Google Scholar 

  • Toulany M, Dittmann K, Krüger M, Baumann M and Rodemann HP 2005 Radioresistance of K-RAS mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother. Oncol. 76 143–150

    Article  CAS  Google Scholar 

  • Ueno K, Hirata H, Shahryari V, Deng G, Tanaka Y, Tabatabai ZL, Hinoda Y and Dahiya R 2013 microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer. Br. J. Cancer 108 1659–1667

    Article  CAS  Google Scholar 

  • Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C and Ferracin M 2006 A microRNA expression signature of human solid tumors defines cancer gene targets. Natl. Acad. Sci. U S A 103 2257–2261

    Article  CAS  Google Scholar 

  • Wang X, Li C, Jin H, Wang S, Zhang Y, Tang X and Tang G 2016a Screening miRNAs for early diagnosis of colorectal cancer by small RNA deep sequencing and evaluation in a Chinese patient population. Oncotargets Ther. 9 1159–1166

    CAS  Google Scholar 

  • Wang XJ, Zhang DL, Fu C, Wei BZ and Li GJ 2016b MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1α feedback loop. Eur. Rev. Med. Pharmacol. Sci. 20 2020–2027

    PubMed  Google Scholar 

  • Xu F, Zhang H, Su Y, Kong J, Yu H and Qian B 2014 Up-regulation of microRNA-183-3p is a potent prognostic marker for lung adenocarcinoma of female non-smokers. Clin. Transl. Oncol. 16 980–985

    Article  CAS  Google Scholar 

  • Yan H, Wang S, Yu H, Zhu J and Chen C 2013 Molecular pathways and functional analysis of miRNA expression associated with paclitaxel-induced apoptosis in hepatocellular carcinoma cells. Pharmacology 92 167–174

    Article  CAS  Google Scholar 

  • Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T and Simon HU 2006 Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat. Cell Biol. 8 1124–1132

    Article  CAS  Google Scholar 

  • Yuan D, Li K, Zhu K, Yan R and Dang C 2015 Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer. Cancer Biol. Ther. 16 268–275

    Article  CAS  Google Scholar 

  • Yuan Y, Zhang Y, Han L, Sun S and Shu Y 2018 miR-183 inhibits autophagy and apoptosis in gastric cancer cells by targeting ultraviolet radiation resistance-associated gene. Int. J. Mol. Med. 42 3562–3570

    CAS  PubMed  Google Scholar 

  • Zhang X, Shi H, Lin S, Ba M and Cui S 2015a MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. Oncol. Rep. 34 1557–1564

    Article  CAS  Google Scholar 

  • Zhang Y, Yu J, Liu H, Ma W, Yan L, Wang J and Li G 2015b Novel epigenetic CREB-miR-630 signaling axis regulates radiosensitivity in colorectal cancer. Plos One 10 e0133870

    Article  Google Scholar 

  • Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D, Miller BC, Cadwell K, Delgado MA, Ponpuak M and Green KG 2008 Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 4 458–469

    Article  CAS  Google Scholar 

  • Zhou Z, Yang ZZ, Wang SJ, Zhang L, Luo JR, Feng Y, Yu XL, Chen XX and Guo XM 2017 The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy. Acta Pharmacol. Sin. 38 513

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Emergency Surgery, Chongqing Three Gorges Central Hospital, Wanzhou, Chongqing, 404000, People’s Republic of China

    Sheng Zheng, Yong-Fu Zhong, De-Ming Tan, Yue Xu & Huai-Xiang Chen

  2. Department of Public Health and Management, Chongqing Three Gorges Medical College, Wanzhou, Chongqing, 404120, People’s Republic of China

    Dan Wang

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  1. Sheng Zheng
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  2. Yong-Fu Zhong
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  3. De-Ming Tan
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  4. Yue Xu
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  5. Huai-Xiang Chen
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  6. Dan Wang
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Correspondence to Dan Wang.

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Communicated by Ullas Kolthur-Seetharam.

Corresponding editor: Ullas Kolthur-Seetharam

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Zheng, S., Zhong, YF., Tan, DM. et al. miR-183-5p enhances the radioresistance of colorectal cancer by directly targeting ATG5. J Biosci 44, 92 (2019). https://doi.org/10.1007/s12038-019-9918-y

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