KIF2C promotes the proliferation of hepatocellular carcinoma cells<i> in vitro</i> and <i>in vivo</i>

Gao, Zhongming; Jia, Honglin; Fang, Yu; Guo, Hongwei; Li, Baoyu

doi:10.3892/etm.2021.10528

Cited by 14 publications

(11 citation statements)

References 37 publications

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“…Previous research has revealed that KIF2C is substantially expressed in liver cancer (17,19,26,27), breast cancer (28), endometrial carcinoma (20), lung cancer (29,30), glioma (31), bladder cancer (32), colorectal cancer (33), esophageal squamous cell carcinoma (34), cervical cancer (18), and thyroid cancer (35). The results of our pan-cancer analysis indicated that KIF2C was highly expressed in 28 tumors, including PCa, which was consistent with previous results reported in the literature.…”

Section: Discussionsupporting

confidence: 92%

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer

Zhang

Gao²,

Ye³

et al. 2022

Front. Immunol.

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Prostate cancer (PCa) is one of the most prevalent cancers of the urinary system. In previous research, Kinesin family member 2C (KIF2C), as an oncogene, has been demonstrated to have a key role in the incidence and progression of different cancers. However, KIF2C has not been reported in PCa. We combined data from different databases, including The Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, and the Genomics of Drug Sensitivity in Cancer database, to explore the potential oncogenic role of KIF2C in PCa through a series of bioinformatics approaches, including analysis of the association between KIF2C and prognosis, clinicopathological features, gene mutations, DNA methylation, immune cell infiltration, and drug resistance. The results showed that KIF2C was significantly up-regulated in PCa. High KIF2C expression was associated with age, pathological stage, lymph node metastases, prostate-specific antigen (PSA), and Gleason score and significantly predicted an unfavorable prognosis in PCa patients. Results from Gene Set Enrichment Analysis (GSEA) suggested that KIF2C was involved in the cell cycle and immune response. KIF2C DNA methylation was reduced in PCa and was inversely linked with KIF2C expression. KIF2C was shown to have a strong relationship with the tumor microenvironment (TME), infiltrating cells, and immune checkpoint genes. Furthermore, high KIF2C expression was significantly resistant to a variety of MAPK signaling pathway-related inhibitors. Our study reveals that KIF2C may be a possible predictive biomarker for assessing prognosis in PCa patients with immune infiltration.

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Section: Discussionsupporting

confidence: 92%

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer

Zhang

Gao²,

Ye³

et al. 2022

Front. Immunol.

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“…Cell viability assay and cell cycle distribution analysis demonstrated no significant alterations between the cell lines (Figure S1A,B). These findings are in contrast to two recent publications in thyroid carcinoma and hepatocarcinoma cells, which showed that a knockdown of MCAK leads to a reduced proliferation rate in these cell types [33,34]. This contradiction might be explained because both publications used a transient siRNA transfection system for their experiments or due to a cell type specific effect.…”

Section: Characterization Of Hela/rpe Crispr/dcas9 Sgmcak Knockdown (Crispri) and Overexpression (Crispra) Cell Linescontrasting

confidence: 94%

Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover

Moon

Kreis

Friemel

et al. 2021

Cancers

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The microtubule (MT) cytoskeleton is crucial for cell motility and migration by regulating multiple cellular activities such as transport and endocytosis of key components of focal adhesions (FA). The kinesin-13 family is important in the regulation of MT dynamics and the best characterized member of this family is the mitotic centromere-associated kinesin (MCAK/KIF2C). Interestingly, its overexpression has been reported to be related to increased metastasis in various tumor entities. Moreover, MCAK is involved in the migration and invasion behavior of various cell types. However, the precise molecular mechanisms were not completely clarified. To address these issues, we generated CRISPR/dCas9 HeLa and retinal pigment epithelium (RPE) cell lines overexpressing or downregulating MCAK. Both up- or downregulation of MCAK led to reduced cell motility and poor migration in malignant as well as benign cells. Specifically, it’s up- or downregulation impaired FA protein composition and phosphorylation status, interfered with a proper spindle and chromosome segregation, disturbed the assembly and disassembly rate of FA, delayed cell adhesion, and compromised the plus-tip dynamics of MTs. In conclusion, our data suggest MCAK act as an important regulator for cell motility and migration by affecting the actin-MT cytoskeleton dynamics and the FA turnover, providing molecular mechanisms by which deregulated MCAK could promote malignant progression and metastasis of tumor cells.

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“…The proteins sorted according to the combined score were as follows: CCNB2, CDK1, PLK1, CCNB1, CDC20, KIF2C, RPS27A, AURKB, UBB, and UBA52. Previous research has verified that CCNB2, CCNB1, CDK1, PLK1, CDC20, KIF2C, RPS27A, and AURKB play vital roles in regulating the cell cycle transition, radiosensitivity and cell proliferation in various tumors ( Wang et al, 2014 ; Nie et al, 2020 ; Zou et al, 2020 ; Gao et al, 2021 ; Gheghiani et al, 2021 ; Zhao et al, 2021 ). From the PPI network of GTSE1, we speculate that GTSE1 plays an important role in the cell cycle transition and malignant proliferation of tumors.…”

Section: Resultsmentioning

confidence: 96%

High GTSE1 expression promotes cell proliferation, metastasis and cisplatin resistance in ccRCC and is associated with immune infiltrates and poor prognosis

Lei

Zhang

et al. 2023

Front. Genet.

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Background: Clear cell renal cell carcinoma is the most common and fatal form of kidney cancer, accounting for 80% of new cases. Although it has been reported that GTSE1 is highly expressed in a variety of tumors and associated with malignant progression and poor clinical prognosis, its clinical significance, correlations with immune cell infiltration and biological function in ccRCC are still poorly understood.Methods: The gene expression, clinicopathological features, and clinical significance of GTSE1 were analyzed using multiple databases, including TCGA, GEO, TIMER, and UALCAN Kaplan–Meier survival analysis, gene set enrichment analysis gene ontology enrichment Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Tumor-infiltrating immune cells and immunomodulators were extracted and analyzed using TCGA-KIRC profiles. Protein‒protein interactions were built using the STRING website. The protein level of GTSE1 in ccRCC patients was detected by immunohistochemistry using a ccRCC tissue chip. Finally, MTT assays, colony-formation assays, cell flow cytometry analyses, EdU-staining assays, wound-healing assays, and transwell migration and invasion assays were conducted to assess the biological function of GTSE1 in vitro.Results: GTSE1 was overexpressed in ccRCC tissues and cells, and GTSE1 overexpression was associated with adverse clinical-pathological factors and poor clinical prognosis. Meanwhile, the functional enrichment analysis indicated that GTSE1 and its coexpressed genes were mainly related to the cell cycle, DNA replication, and immunoreaction, such as T-cell activation and innate immune response, through multiple signaling pathways, including the P53 signaling pathway and T-cell receptor signaling pathway. Furthermore, we observed a significant relationship between GTSE1 expression and the levels of infiltrating immune cells in ccRCC. Biological functional studies demonstrated that GTSE1 could promote the malignant progression of ccRCC by promoting cell proliferation, cell cycle transition, migration, and invasion capacity and decreasing the sensitivity of ccRCC cells to cisplatin.Conclusion: Our results indicate that GTSE1, serving as a potential oncogene, can promote malignant progression and cisplatin resistance in ccRCC. Additionally, high GTSE1 expression contributes to an increased level of immune cell infiltration and is associated with a worse prognosis, providing a potential target for tumor therapy in ccRCC.

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KIF2C promotes the proliferation of hepatocellular carcinoma cells in vitro and in vivo

Cited by 14 publications

References 37 publications

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer

Large-Scale Transcriptome Data Analysis Identifies KIF2C as a Potential Therapeutic Target Associated With Immune Infiltration in Prostate Cancer

Mitotic Centromere-Associated Kinesin (MCAK/KIF2C) Regulates Cell Migration and Invasion by Modulating Microtubule Dynamics and Focal Adhesion Turnover

High GTSE1 expression promotes cell proliferation, metastasis and cisplatin resistance in ccRCC and is associated with immune infiltrates and poor prognosis

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