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Human Cell

pp 1–12 | Cite as

miR-663b promotes colorectal cancer progression by activating Ras/Raf signaling through downregulation of TNK1

  • Sen Hong
  • Zhenkun Yan
  • Helei WangEmail author
  • Lei DingEmail author
  • Yumei Song
  • Miaomiao Bi
Research Article

Abstract

MiR-663b has been demonstrated to be abnormally expressed in several cancer types and was involved in the progression of cancer. Although overexpression of miR-663b in colorectal cancer was observed, the role of miR-663b in colorectal cancer cells has not been identified yet. In this study, we analyzed expression of miR-663b in colorectal tumors and explored the molecular mechanism of miR-663b in colorectal cancer cells. MiR-663b was significantly overexpressed in colorectal tumors and cell lines. Downregulation of miR-663b inhibited cell proliferation and sphere forming ability in colorectal cancer cells. In addition, miR-663b downregulation inactivated Ras/Raf signaling activity and subsequently decreased YAP1 and CD44 expression in colorectal cancer cells. Using TargetScan software, TNK1, a negative regulator of Ras/Raf signaling, was predicted to be a target gene of miR-663b. Western blotting and RT-qPCR showed that TNK1 expression was negatively regulated by miR-663b. In addition, the direct binding of miR-663b to TNK1 mRNA was proved by dual luciferase reporter assay. Furthermore, downregulation of miR-663b inhibited colorectal cancer cell proliferation and stemness, which was reversed after siRNA-mediated silencing of TNK1. In conclusion, the current study revealed a pivotal role of miR-663b in the progression of colorectal cancer.

Keywords

microR-663b TNK1 Colorectal cancer 

Notes

Author contributions

SH, ZY and HW participated in the design and performance of the experiments; SH, ZY, HW, YS and MB contributed to the collection of samples and clinical data; ZY and HW analyzed the data; HW and LD supervised and wrote the manuscript.

Compliance with ethical standards

Conflict of interest

We declare that we have no conflict of interest in the current study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of The First Hospital of Jilin University (No. FHJU20120603) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Colorectal and Anal SurgeryThe First Hospital of Jilin UniversityChangchunPeople’s Republic of China
  2. 2.Department of Endoscopy CenterChina-Japan Union Hospital of Jilin UniversityChangchunPeople’s Republic of China
  3. 3.Department of Gastrointestinal SurgeryThe First Hospital of Jilin UniversityChangchunPeople’s Republic of China
  4. 4.Department of RadiologyChina-Japan Union Hospital of Jilin UniversityChangchunPeople’s Republic of China
  5. 5.Department of Thoracic OncologyTumor Hospital of Jilin ProvinceChangchunPeople’s Republic of China
  6. 6.Department of OphthalmologyThe China-Japan Union Hospital of Jilin University, Jilin UniversityChangchunPeople’s Republic of China

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