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Tumor Biology

, Volume 37, Issue 6, pp 7657–7665 | Cite as

Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner

  • Tianzhen Wang
  • Peng Han
  • Yan He
  • Ci Zhao
  • Guangyu Wang
  • Weiwei Yang
  • Ming Shan
  • Yuanyuan Zhu
  • Chao Yang
  • Mingjiao Weng
  • Di Wu
  • Lin Gao
  • Xiaoming Jin
  • Yunwei Wei
  • BinBin Cui
  • Guomin Shen
  • Xiaobo Li
Original Article

Abstract

RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.

Keywords

Colon cancer Lin28A Chemosensitivity Apoptosis H2AX 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81302061 to Tianzhen Wang, Grant No. 81401961 to Xiaobo Li, Grant No. 81302388 to Lin Gao, and Grant No. 31301076 to Guomin Shen), Postdoctoral Scientific Research Development Fund of Heilongjiang Province (Grant No. LBH-Q14104 to Xiaobo Li), and Wu-Lian-De Youth Science Foundation of Harbin Medical University (Grant No.WLD-QN1411 to Xiaobo Li).

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of PathologyHarbin Medical UniversityHarbinChina
  2. 2.Department of Colorectal SurgeryThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of Gastrointestinal Medical OncologyThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina
  4. 4.Department of Breast SurgeryThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina
  5. 5.Department of Obstetrics and GynecologyFirst Affiliated Hospital of Harbin Medical UniversityHarbinChina
  6. 6.Center for Endemic Disease Control, Chinese Center for Disease Control and PreventionHarbin Medical UniversityHarbinChina
  7. 7.Department of General SurgeryThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina
  8. 8.Department of Medical Genetics, Medical CollegeHenan University of Science and TechnologyLuoyangChina

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