Skip to main content
Log in

miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7

  • Original Paper
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3′UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2016) Global patterns and trends in colorectal cancer incidence and mortality. Gut

  2. Baquero P, Karvela M, Mitchell R, Mukhopadhyay A, Pellicano F, Hopcroft L, Holyoake TL, Helgason G V (2015) The autophagy related protein ATG7 regulates differentiation and energy metabolism of CML cells. Br J Haematol 6

  3. Bovell LC, Shanmugam C, Putcha BD, Katkoori VR, Zhang B, Bae S, Singh KP, Grizzle WE, Manne U (2013) The prognostic value of microRNAs varies with patient race/ethnicity and stage of colorectal cancer. Clin Cancer Res 19:3955–3965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Brody H (2015) Colorectal cancer. Nature 521:S1

    Article  CAS  PubMed  Google Scholar 

  5. Catela IT, Aralica G, Cacev T, Loncar B, Kapitanovic S (2013) miR-106a overexpression and pRB downregulation in sporadic colorectal cancer. Exp Mol Pathol 94:148–154

    Article  Google Scholar 

  6. Chang TK, Shravage BV, Hayes SD, Powers CM, Simin RT, Wade HJ, Baehrecke EH (2013) Uba1 functions in Atg7- and Atg3-independent autophagy. Nat Cell Biol 15:1067–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen WY, Zhao XJ, Yu ZF, Hu FL, Liu YP, Cui BB, Dong XS, Zhao YS (2015) The potential of plasma miRNAs for diagnosis and risk estimation of colorectal cancer. Int J Clin Exp Pathol 8:7092–7101

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Comincini S, Allavena G, Palumbo S, Morini M, Durando F, Angeletti F, Pirtoli L, Miracco C (2013) 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 14:574–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ergun M, Eyigor S, Karaca B, Kisim A, Uslu R (2013) Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients. Eur J Cancer Care (Engl) 22:626–637

    Article  CAS  Google Scholar 

  10. Gómez-Puerto MC, Folkerts H, Wierenga ATJ, Schepers K, Schuringa JJ, Coffer PJ, Vellenga E (2016) Autophagy proteins ATG5 and ATG7 are essential for the maintenance of human CD34+ hematopoietic stem-progenitor cells. Stem Cells

  11. Hao H, Liu L, Zhang D, Wang C, Xia G, Zhong F, Hu X (2016) Diagnostic and prognostic value of miR-106a in colorectal cancer. Oncotarget. doi:10.18632/oncotarget.13766

    Google Scholar 

  12. Hofius D, Schultz-Larsen T, Joensen J, Tsitsigiannis DI, Petersen NH, Mattsson O, Jorgensen LB, Jones JD, Mundy J, Petersen M (2009) Autophagic components contribute to hypersensitive cell death in Arabidopsis. Cell 137:773–783

    Article  CAS  PubMed  Google Scholar 

  13. Hsieh YY, Lo HL, Yang PM (2016) EZH2 inhibitors transcriptionally upregulate cytotoxic autophagy and cytoprotective unfolded protein response in human colorectal cancer cells. Am J Cancer Res 6:1661–1680

    PubMed  PubMed Central  Google Scholar 

  14. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y (2005) Impairment of starvation-induced and constitutive autophagy in Atg7. J Cell Biol 169:425–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ma HL, Wen XP, Zhang XZ, Wang XL, Zhao DL, Che SM, Dang CX (2015) miR-106a* inhibits the proliferation of esophageal carcinoma cells by targeting CDK2-associated Cullin 1 (CACUL1). Cell Mol Biol (Noisy-le-grand) 61:56–62

  16. Masui A, Hamada M, Kameyama H, Wakabayashi K, Takasu A, Imai T, Iwai S, Yura Y (2016) Autophagy as a survival mechanism for squamous cell carcinoma cells in endonuclease G-mediated apoptosis. PLoS One 11:e162786

    Article  Google Scholar 

  17. Mccoy F, Hurwitz J, Mctavish N, Paul I, Barnes C, O’Hagan B, Odrzywol K, Murray J, Longley D, Mckerr G (2009) Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK. Cell Death Dis 1:e108

    Article  Google Scholar 

  18. Moscat J, Diaz-Meco MT (2009) p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 137:1001–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Qi L, Bart J, Tan LP, Platteel I, Sluis TVD, Huitema S, Harms G, Fu L, Hollema H, Berg AVD (2009) Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer 9:163

    Article  PubMed  PubMed Central  Google Scholar 

  20. Qiu Y, Yuan R, Zhang S, Chen L, Huang D, Hao H, Shao J (2015) Rock2 stabilizes beta-catenin to promote tumor invasion and metastasis in colorectal cancer. Biochem Biophys Res Commun 467:629–637

    Article  CAS  PubMed  Google Scholar 

  21. Wang R, Li Y, Hou Y, Yang Q, Chen S, Wang X, Wang Z, Yang Y, Chen C, Wang Z et al (2015) The PDGF-D/miR-106a/Twist1 pathway orchestrates epithelial-mesenchymal transition in gemcitabine resistance hepatoma cells. Oncotarget 6:7000–7010

  22. Wang Z, Liu M, Zhu H, Zhang W, He S, Hu C, Quan L, Bai J, Xu N (2013) miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog 52:634–646

    Article  CAS  PubMed  Google Scholar 

  23. Yang G, Zhang R, Chen X, Mu Y, Ai J, Shi C, Liu Y, Shi C, Sun L, Rainov N G et al (2011) MiR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl) 89:1037–1050

  24. Yang G, Zhang R, Chen X, Mu Y, Ai J, Shi C, Liu Y, Shi C, Sun L, Rainov NG et al (2011) MiR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl) 89:1037–1050

  25. Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, Baehrecke EH, Lenardo MJ (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500–1502

    Article  CAS  PubMed  Google Scholar 

  26. Yuan R, Zhi Q, Zhao H, Han Y, Gao L, Wang B, Kou Z, Guo Z, He S, Xue X et al (2015) Upregulated expression of miR-106a by DNA hypomethylation plays an oncogenic role in hepatocellular carcinoma. Tumour Biol 36:3093–3100

    Article  CAS  PubMed  Google Scholar 

  27. Zeng Y, Gang H, Mo Y, Wang W, Hong C (2015) MIR137 regulates starvation-induced autophagy by targeting ATG7. J Mol Neurosci 56:815–821

    Article  CAS  PubMed  Google Scholar 

  28. Zhang Y, Lu Q, Cai X (2013) MicroRNA-106a induces multidrug resistance in gastric cancer by targeting RUNX3. FEBS Lett 587:3069–3075

    Article  CAS  PubMed  Google Scholar 

  29. Zhu M, Zhang N, He S, Yan R, Zhang J (2016) MicroRNA-106a functions as an oncogene in human gastric cancer and contributes to proliferation and metastasis in vitro and in vivo. Clin Exp Metastasis 33:509–519

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Haibin Hao.

Ethics declarations

Conflict of interest

The authors have no conflicts to disclose.

Ethics statement

The study has been approved by the Ethics Committee of our institution that conforming to the provisions of the Declaration of Helsinki.

Additional information

Haibin Hao, Guangfeng Xia, and Chao Wang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, H., Xia, G., Wang, C. et al. miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7. Med Mol Morphol 50, 76–85 (2017). https://doi.org/10.1007/s00795-016-0150-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-016-0150-7

Keywords

Navigation