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

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...

Full description

Bibliographic Details
Main Authors: Hanpu Zhang, Chenyuan Li, Shichong Liao, Yi Tu, Shengrong Sun, Feng Yao, Zhiyu Li, Zhong Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Cancer Biology & Therapy
Subjects:
Online Access:http://dx.doi.org/10.1080/15384047.2022.2125260
_version_ 1797404030531534848
author Hanpu Zhang
Chenyuan Li
Shichong Liao
Yi Tu
Shengrong Sun
Feng Yao
Zhiyu Li
Zhong Wang
author_facet Hanpu Zhang
Chenyuan Li
Shichong Liao
Yi Tu
Shengrong Sun
Feng Yao
Zhiyu Li
Zhong Wang
author_sort Hanpu Zhang
collection DOAJ
description 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.
first_indexed 2024-03-09T02:47:13Z
format Article
id doaj.art-4818dd66f2db46008a876e186a5932ab
institution Directory Open Access Journal
issn 1538-4047
1555-8576
language English
last_indexed 2024-03-09T02:47:13Z
publishDate 2022-12-01
publisher Taylor & Francis Group
record_format Article
series Cancer Biology & Therapy
spelling doaj.art-4818dd66f2db46008a876e186a5932ab2023-12-05T15:58:14ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762022-12-0123111110.1080/15384047.2022.21252602125260PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancerHanpu Zhang0Chenyuan Li1Shichong Liao2Yi Tu3Shengrong Sun4Feng Yao5Zhiyu Li6Zhong Wang7Renmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityRenmin Hospital of Wuhan UniversityThe 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.http://dx.doi.org/10.1080/15384047.2022.2125260psmd12kif15mekerkhepatocellular carcinoma
spellingShingle Hanpu Zhang
Chenyuan Li
Shichong Liao
Yi Tu
Shengrong Sun
Feng Yao
Zhiyu Li
Zhong Wang
PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer
Cancer Biology & Therapy
psmd12
kif15
mek
erk
hepatocellular carcinoma
title PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer
title_full PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer
title_fullStr PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer
title_full_unstemmed PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer
title_short PSMD12 promotes the activation of the MEK-ERK pathway by upregulating KIF15 to promote the malignant progression of liver cancer
title_sort psmd12 promotes the activation of the mek erk pathway by upregulating kif15 to promote the malignant progression of liver cancer
topic psmd12
kif15
mek
erk
hepatocellular carcinoma
url http://dx.doi.org/10.1080/15384047.2022.2125260
work_keys_str_mv AT hanpuzhang psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT chenyuanli psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT shichongliao psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT yitu psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT shengrongsun psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT fengyao psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT zhiyuli psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer
AT zhongwang psmd12promotestheactivationofthemekerkpathwaybyupregulatingkif15topromotethemalignantprogressionoflivercancer