Salt-inducible kinase 2 functions as a tumor suppressor in hepatocellular carcinoma.


Journal

Environmental toxicology
ISSN: 1522-7278
Titre abrégé: Environ Toxicol
Pays: United States
ID NLM: 100885357

Informations de publication

Date de publication:
Dec 2021
Historique:
revised: 08 08 2021
received: 14 03 2021
accepted: 29 08 2021
pubmed: 8 9 2021
medline: 5 11 2021
entrez: 7 9 2021
Statut: ppublish

Résumé

Salt-inducible kinase 2 (SIK2) has been reported to be involved in cancer progression in a dichotomous manner. However, the role and mechanism of action of SIK2 in hepatocellular carcinoma (HCC) progression remain elusive. SIK2 expression in HCC tissues in The Cancer Genome Atlas (TCGA) database was analyzed using the AIPuFu platform. SIK2 expression in HCC cells was examined by quantitative real-time PCR and western blot analysis. The expression of N-cadherin, E-cadherin, β-catenin, and c-Myc was detected by western blot analysis. SIK2 was downregulated in HCC tissues compared with normal patients, and low SIK2 expression was correlated with poor prognosis in HCC patients in TCGA database. SIK2 was lowly expressed in HCC cells than that in normal human liver epithelial cells. SIK2 overexpression inhibited cell proliferation and invasion and promoted apoptosis in HCC cells, while SIK2 silencing exerted the opposite effects. Additionally, SIK2 overexpression inactivated the Wnt/β-catenin pathway in HCC cells, as evidenced by the reduced expression of β-catenin and c-Myc. β-catenin overexpression rescued the inhibitory effects of SIK2 on the malignant properties of HCC cells. Xenograft tumor experiment confirmed that SIK2 suppressed the growth of HCC cells in vivo. In conclusion, SIK2 exerted anti-tumor activity in HCC via inactivating the Wnt/β-catenin signaling pathway.

Identifiants

pubmed: 34491613
doi: 10.1002/tox.23366
doi:

Substances chimiques

beta Catenin 0
salt-inducible kinase-2, human EC 2.7.1.-
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2530-2540

Subventions

Organisme : Joint Construction Project of Henan Medical Science and Technology Plan
ID : LHGJ20200902

Informations de copyright

© 2021 Wiley Periodicals LLC.

Références

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Auteurs

Yuan Li (Y)

Department of General Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, China.

Jinsong Yu (J)

Department of General Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, China.

Manran Jia (M)

Department of General Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, China.

Pei Ma (P)

Department of General Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, China.

Chunrong Dong (C)

Department of Oncology, The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

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