PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer

Hanpu Zhang; Chenyuan Li; Shichong Liao; Yi Tu; Shengrong Sun; Feng Yao; Zhiyu Li; Zhong Wang

doi:10.1080/15384047.2022.2125260

PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer

Cancer Biol Ther. 2022 Dec 31;23(1):1-11. doi: 10.1080/15384047.2022.2125260.

Authors

Hanpu Zhang^{1

2}, Chenyuan Li¹, Shichong Liao¹, Yi Tu¹, Shengrong Sun¹, Feng Yao¹, Zhiyu Li¹, Zhong Wang¹

Affiliations

¹ Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, P. R. China.
² Department of Colorectal Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

The tumor recurrence and drug resistance of hepatocellular carcinoma (HCC) threatened patients a lot. The mechanism should be further explored. The information of expression status and survival were available in public databases. The Western blot and immunohistochemistry staining displayed the level of related proteins. CCK-8, colony-formation assays, transwell assay and wound healing assay were performed to illustrate the ability of tumor growth, invasion and migration. In vivo model was established to verify our cell experiments. In our study, we revealed that proteasome 26S subunit, non-ATPase 12 (PSMD12) was high expressed in HCC tissues and positive related to the survival. In vitro experiments suggested that PSMD12 knockdown attenuated tumor cell growth, invasion and migration. Moreover, PSMD12 interference blocked the activation of MEK-ERK pathway. The ERK inhibitor could alleviate the tumor-promoting effect in PSMD12-overexpression cells. In addition, kinesin family member 15 (KIF15) was also observed to be highly expressed in HCC and be harmful to the survival. The public database, the images of immunohistochemistry and the western blot illustrated that PSMD12 and KIF15 was positive correlated. KIF15 knockdown impaired tumor progression and tumor-promoting effect of PSMD12. The xenograft models supported the results of cell experiments. In conclusion, PSMD12 could activated MEK-ERK pathway via KIF15 upregulation, thereby promoting tumor progression.

Keywords: ERK; KIF15; MEK; PSMD12; hepatocellular carcinoma.

MeSH terms

Carcinoma, Hepatocellular* / pathology
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation, Neoplastic
Humans
Kinesins / genetics
Liver Neoplasms* / pathology
MAP Kinase Signaling System
Neoplasm Recurrence, Local
Proteasome Endopeptidase Complex / metabolism
Sincalide / metabolism

Substances

KIF15 protein, human
Proteasome Endopeptidase Complex
Kinesins
Sincalide

Grants and funding

This work was partially supported by a National Natural Science Foundation of China (NSFC) grant (grant no. 82203374) and Fundamental Research Funds for the Central Universities (2042022kf1081) to Dr. Wang Zhong, the Natural Science Foundation of Hubei Province (2020CFA026) by Prof. Yi Tu, a National Natural Science Foundation of China (NSFC) grant (grant No.: 81471781) and a National Major Scientific Instruments and Equipment Development Projects grant (grant No.: 2012YQ160203) to Prof. Shengrong Sun.