Dataset Information

Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway.

ABSTRACT: The present study aimed to explore the prognostic value and role of kinesin family member 4A (KIF4A) expression in human osteosarcoma. KIF4A expression was evaluated in human osteosarcoma tissues from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Reverse transcription-quantitative PCR was then applied to assess KIF4A level in both osteosarcoma cell lines and tissues. The association between KIF4A expression and clinical results in patients with osteosarcoma was detected by survival analysis. MTT assays and colony formation assays were used to evaluate the effects of KIF4A on osteosarcoma cell proliferation. The results indicated that the level of KIF4A was increased and associated with a poor prognosis in osteosarcoma tissues. Knockdown of KIF4A was shown to inhibit osteosarcoma cellular proliferation by affecting the MAPK pathway. The level of KIF4A was high in the human osteosarcoma tissues and this could be considered as a tumor induction gene, which may be used as an indicator of prognosis.

SUBMITTER: Zhu D

PROVIDER: S-EPMC8495555 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway.

Zhu Dongsheng D Xu Xiangfei X Zhang Ming M Wang Tong T

Experimental and therapeutic medicine 20210922 5

The present study aimed to explore the prognostic value and role of kinesin family member 4A (KIF4A) expression in human osteosarcoma. KIF4A expression was evaluated in human osteosarcoma tissues from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Reverse transcription-quantitative PCR was then applied to assess KIF4A level in both osteosarcoma cell lines and tissues. The association between KIF4A expression and clinical results in patients with osteosarcoma was detected by surviv ...[more]

PMID: 34630693

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Project description:BackgroundMitogen-activated protein kinase 4 (MAPK4) is an atypical member of the mitogen-activated protein kinase (MAPK) family. We report here that MAPK4 is overexpressed in glioma. The clinical significance, biological roles and underlying molecular mechanisms through which MAPK4 acts in glioma remain unclear.MethodsAnalysis of MAPK4 expression and associated survival in glioma patients was performed based on data obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases and confirmed in human glioma tissue by immunohistochemistry. MAPK4 function and pathway enrichment were analyzed through Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO). The viability and migration ability of MAPK4-silenced glioblastoma multiforme (GBM) cells were evaluated using CCK8 and transwell assays, respectively, and cell cycle and apoptosis analyses were performed using flow cytometry. Immunoblotting was used to analyze the protein level in MAPK4 knockdown glioma cells. We also analyzed the correlation of MAPK4 expression with immune infiltration and immune checkpoints in glioma.ResultsMAPK4 was overexpressed in IDH wild-type (wt) and 1p/19q non-codeletion gliomas. MAPK4 expression predicted poor prognosis of glioma patients. MAPK4 was significantly related to functional states, including stemness, metastasis, cell cycle, differentiation and proliferation, in glioma at single-cell resolution. MAPK4 silencing inhibited proliferation and migration and induced G1 cell cycle arrest in glioma cells via the AKT/mTOR pathway. In vivo, MAPK4 knockdown markedly suppressed the growth of primary glioma. In addition, MAPK4 expression correlated negatively with the infiltration of plasmacytoid DC cells, CD8+ T cells and T helper cells. Moreover, MAPK4 expression correlated positively with expression of the main immunoinhibitor checkpoint molecules and some chemokines in glioma.ConclusionMAPK4 functions as a prognostic indicator in glioma and promotes the proliferation and migration of GBM cells through the AKT/mTOR pathway. MAPK4 may participate in immune infiltration and the expression of immune checkpoints in the glioma microenvironment.

Project description:Background: Many transcription factors involved in embryonic development and reactivated in tumors are considered potential prognostic biomarkers and novel therapeutic targets in various cancers. Sine oculis homeobox homolog 1 (SIX1), a developmentally restricted transcriptional regulator, plays a critical role during tumor initiation and development. However, the prognostic value and biological function of SIX1 in non-small cell lung cancer (NSCLC) remain unclear. Methods: Bioinformatic analyses were conducted to investigate the expression of SIX1 in cancer and adjacent normal tissues of NSCLC and further explore the correlations between SIX1 expression and clinical outcomes. Western blotting and RT-PCR analysis were performed to detect of SIX1 expression level in NSCLC cell lines and normal bronchial epithelial cell. EdU, CCK-8, clonal formation assay, wound healing and transwell assay were performed to explore the effects of gain- or loss-of-function of SIX1 on cellular proliferation, migration and invasion in vitro. Gene set enrichment analysis (GSEA) was used to identify the potential signaling pathways involved in SIX1 mediated biological function and the correlation was confirmed by western blotting and RT-PCR analysis. In vivo experiment was conducted to further validate the tumor-promoting effects of SIX1. Results: Bioinformatic analysis indicated that SIX1 was markedly upregulated in NSCLC tissues of and positively correlated with poor prognosis of patients with NSCLC. Ectopic expression of SIX1 facilitated proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. On the contrary, knocking down SIX1 exhibited the opposite effects. Mechanistic studies suggested that SIX1 activated the Notch pathway to promote the malignant biological behaviors of NSCLC, which could be reversed by inhibiting the Notch signaling with γ-secretase inhibitor. Conclusions: SIX1 could facilitate multiple malignant biological behaviors by activating the Notch signaling pathway and function as a promising prognostic biomarker.

Dataset Information

Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway.

Publications

Enhanced expression of KIF4A in osteosarcoma predicts a poor prognosis and facilitates tumor growth by activation of the MAPK pathway.

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