KIF2A promotes the progression via AKT signaling pathway and is upregulated by transcription factor ETV4 in human gastric cancer

Zhang, Xin; Wang, Yuyan; Liu, Xiumei; Zhao, Anqi; Yang, Zhongheng; Kong, Fanshuang; Sun, Lili; Yu, Yingyu; Jiang, Li-Peng

doi:10.1016/j.biopha.2020.109840

Cited by 28 publications

(31 citation statements)

References 31 publications

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“…It was reported that MTMR2 mediated epithelial-mesenchymal transition through the IFNγ/STAT1/IRF1 pathway to promote GC invasion and metastasis [ 62 ]. KIF2A expression is a potential target for GC therapy, which can be upregulated by transcription factor ETV4 [ 63 ]. Krüppel-like factors (KLFs) have been extensively investigated in multi-cancers, which plays a significant role in GC progression and could be a new therapeutic target for GC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis

Zhang

et al. 2021

BMC Cancer

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Background Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. Methods Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. Conclusions We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

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Section: Discussionmentioning

confidence: 99%

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis

Zhang

et al. 2021

BMC Cancer

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“…KIF2A together with KIF2B and KIF2C constituted KIFs family in human, and these three membranes were highly conserved in their primary sequences but displayed distinct localization and nonoverlapping functions [ 28 ]. KIF2A was located in centrosomes [ 28 ], and had been discovered to be oncogenic in multiple cancer progressions [ 29–31 ]. Here, we showed that KIF2A downregulation was the common result between blocking circ_0010235 and re-expressing miR-338-3p in curbing NSCLC proliferation, migration and invasion phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Zhu

et al. 2021

Annals of Medicine

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Background Circular RNA microarray analysis showed hsa_circ_0010235 (circ_0010235) was highly upregulated in non-small-cell lung cancer (NSCLC) patients; however, its role in carcinogenesis and development of NSCLC cells was unrevealed. Here, we intended to investigate role and mechanism of circ_0010235 in NSCLC proliferation, migration and invasion. Methods and results Expression of circ_0010235, microRNA (miR)-338-3p and kinesin family member 2A (KIF2A) was detected by quantitative real-time PCR, western blotting and immunohistochemistry (IHC). Cell progression was measured by cell-counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) assay, flow cytometry, transwell assay, western blotting, IHC and xenograft experiment. The relationship among circ_0010235, miR-338-3p and KIF2A was determined by dual-luciferase reporter assay, RNA immunoprecipitation and Pearson’s correlation analysis. Expression of circ_0010235 was increased in human NSCLC tissues and cells, accompanied with miR-338-3p downregulation and KIF2A upregulation. Essentially, circ_0010235 could sponge miR-338-3p via target binding, and miR-338-3p downstream targeted KIF2A. Functionally, exhaustion of circ_0010235 induced apoptosis rate of NSCLC cells and curbed cell viability, EdU incorporation, migration rate and invasion rate, accompanied with higher E-cadherin and lower N-cadherin expression. Additionally, re-expression of miR-338-3p prompted above similar effects in NSCLC cells in vitro . Contrarily, miR-338-3p blockage partially counteract the effects of circ_0010235 exhaustion; plus, restoration of KIF2A could attenuate miR-338-3p role, as well. Notably, interfering circ_0010235 delayed tumour growth of NSCLC cells by promoting miR-338-3p and E-cadherin expression, and depressing KIF2A, ki-67 and N-cadherin expression. Conclusions circ_0010235 could be a novel identified oncogenic circRNA in NSCLC, and targeting miR-338-3p/KIF2A axis was one regulatory mechanism underlying circ_0010235. KEY MESSAGE Circ_0010235 was an upregulated circRNA in NSCLC patients and cells. Interfering circ_0010235 restrained NSCLC cell proliferation and metastasis in vitro and in vivo . miR-338-3p per se suppressed NSCLC in vitro and its downregulation diminished the tumour-suppressive role of circ_0010235 blockage in NSCLC cells. miR-338-3p could downstream target KIF2A and be sponged by circ_0010235.

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“…Additionally, previous studies have already reported the correlation between KIF2A inactivation and induced apoptosis in cancer cells ( Zhang et al, 2016 , 2019 ; Li et al, 2019 ). The silencing of KIF2A by siRNA resulted in a decrease of PI3 kinase/Akt expression and downstream proteins, a key signaling pathway involved in the regulation of cell proliferation and growth, and ultimately in the initiation of apoptosis ( Wang et al, 2014 ; Zhang et al, 2020 ). In addition, the neuroprotective role of the PI3 kinase/Akt signaling pathway in zebrafish has already been elucidated, emphasizing its function in the attainment of normal brain size during zebrafish embryogenesis ( Chen et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Modeling Neurodevelopmental Disorders and Epilepsy Caused by Loss of Function ofkif2ain Zebrafish

Partoens

Meulemeester

Giong

et al. 2021

eNeuro

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KIF2A promotes the progression via AKT signaling pathway and is upregulated by transcription factor ETV4 in human gastric cancer

Cited by 28 publications

References 31 publications

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis

Circular RNA circ_0010235 sponges miR-338-3p to play oncogenic role in proliferation, migration and invasion of non-small-cell lung cancer cells through modulating KIF2A

Modeling Neurodevelopmental Disorders and Epilepsy Caused by Loss of Function ofkif2ain Zebrafish

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