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The pro-survival function of DLEC1 and its protection of cancer cells against 5-FU-induced apoptosis through up-regulation of BCL-XL

  • Guo-Hua QiuEmail author
  • Wutang Que
  • Shanying Yan
  • Xintian Zheng
  • Xiaojin Xie
  • Cuiqin Huang
  • Xiaoyan Yang
  • Shing Chuan HooiEmail author
Original Article
  • 17 Downloads

Abstract

The tumor suppressor DLEC1 has been shown to promote cell proliferation when AP-2α2 is down-regulated in HCT116 stable clones, suggesting its pro-survival nature. However, the pro-survival function of DLEC1 has not been confirmed in other cells and its underlying mechanisms remain elusive. Therefore, we knocked down DLEC1 in a panel of cell lines and found that DLEC1 depletion caused various extents of cell death through intrinsic pathway. DLEC1 overexpression promoted cell survival and reduced cell death in cancer cells after 5-FU treatment, while DLEC1 down-regulation sensitized cancer cells to 5-FU. Further studies demonstrated that DLEC1 attenuated the increase in cleaved PARP, caspase-3 and caspase-7, the activity of caspase-9 and the diffusion of cytosolic cytochrome c from mitochondria. Our data also showed that BCL-XL was up-regulated by DLEC1 in stable clones after 5-FU treatment. Altogether, these results indicated that DLEC1 protects cells against cell death induced by 5-FU through the attenuation of active proteins in caspase cascade and the up-regulation of BCL-XL. Therefore, DLEC1 can be a pro-survival protein under certain circumstances and a potential therapeutic target for increasing sensitivity of cancer cells to 5-FU.

Keywords

DLEC1 Cell lines Pro-survival Intrinsic apoptosis 5-FU BCL-XL 

Notes

Acknowledgements

This study was supported by the Major Project of Fujian Provincial Science and Technology Department (2014NZ0002-3), Longyan Science and Technology Scheme (2017LY73), Natural Science Foundation of Fujian Province (2018J01456) and the National University of Singapore ARF Grants R-185-000-074-112 and R-185-000-087-112.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Fujian Provincial Key Laboratory for the Prevention and Control of Animal Infectious Diseases and BiotechnologyLongyan UniversityLongyanPeople’s Republic of China
  2. 2.Key Laboratory of Preventive Veterinary Medicine and Biotechnology, Fujian Province UniversitiesLongyan UniversityLongyanPeople’s Republic of China
  3. 3.College of Life SciencesLongyan UniversityLongyanPeople’s Republic of China
  4. 4.Department of Physiology, Faculty of MedicineNational University of SingaporeSingaporeSingapore
  5. 5.Orthopedics DepartmentLongyan First HospitalLongyanPeople’s Republic of China

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