KIF26B, a novel oncogene, promotes proliferation and metastasis by activating the VEGF pathway in gastric cancer

Zhang, H; Rr, Ma; Wang, Xiujun; Zx, Su; Chen, X; Db, Shi; Guo, X-Y; Ht, Liu; Gao, Pu

doi:10.1038/onc.2017.163

Cited by 61 publications

(57 citation statements)

References 35 publications

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“…Furthermore, except for proliferation and apoptosis play vital roles in GC, invasion and metastasis are important causes of poor prognosis of GC. Kinesin family member 26B (KIF26B) is a novel oncogene upregulated in metastatic GC tissues, and it could promote metastasis via VEGF pathway in GC [44]. However, no report has been published on whether KIF15 is related to the invasion and metastasis of GC so far.…”

Section: Discussionmentioning

confidence: 99%

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

Ding

et al. 2020

Cancer Cell Int

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Background: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. Methods: GC patients' data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan-Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients' prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. Results: The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan-Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. Conclusions: Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

Ding

et al. 2020

Cancer Cell Int

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“…For staining area scoring: 0% = 0, 1–25% = 1, 26–50% = 2, 51–75% = 3 and 76–100% = 4. These scores were multiplied to produce the final score: 0–1, negative expression; 2–4, weak positive expression; 6–12, strong positive expression [46]. …”

Section: Methodsmentioning

confidence: 99%

C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation

Zhao

Qiu

et al. 2018

Oncogene

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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo. Our results found that the expression of KLF5, GCN5, GDF15, C5aR, and C5a was significantly upregulated in NSCLC patients. Mechanistic exploration in vitro revealed that C5a could facilitate A549 cell proliferation through increasing KLF5, GCN5, and GDF15 expression. Besides, KLF5 and GCN5 could form a complex, binding to GDF15 promoter in a KLF5-dependent manner and leading to GDF15 gene transcription. More importantly, GCN5-mediated KLF5 acetylation contributing to GDF15 gene transcription and cell proliferation upon C5a stimulation, the region (−103 to +58 nt) of GDF15 promoter which KLF5 could bind to, and two new KLF5 lysine sites (K335 and K391) acetylated by GCN5 were identified for the first time. Furthermore, our experiment in vivo demonstrated that the growth of xenograft tumors in BALB/c nude mice was greatly suppressed by the silence of KLF5, GCN5, or GDF15. Collectively, these findings disclose that C5a-driven KLF5–GCN5–GDF15 axis had a critical role in NSCLC proliferation and might serve as targets for NSCLC therapy.

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“…Wang et al[ 9 ] found that KIF15 can promote the proliferation, invasion, and metastasis of pancreatic cancer cells through the MEK–ERK signaling pathway. Zhang et al[ 10 ] reported that KIF26B promoted the development of GC by activating the vascular endothelial growth factor pathway. Chen et al[ 10 ] confirmed that KIF4B is an independent prognostic factor for hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of KIF23 expression in gastric cancer

Liang

Liu

Huang

et al. 2020

WJGO

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BACKGROUND Kinesin super family 23 (KIF23) is a member of the KIF family, and it plays an important role in mitosis and cytokinesis. Loss of expression can cause mitotic arrest. The Oncomine database is one of the largest oncogene chip databases in the world, and is an integrated data mining platform for cancer gene information. By querying the database, differences in expression between tumor tissue and normal tissue can be determined. AIM To study the expression and prognostic significance of KIF23 in gastric cancer (GC). METHODS We used immunohistochemistry to compare the expression of KIF23 in GC and normal gastric tissues. We mined the data on the expression and prognosis of KIF23 in GC using Oncomine and Kaplan–Meier plotter database. RESULTS Compared with normal gastric tissues, KIF23 expression was increased in GC tissues, and correlated with T, N, and tumor–node–metastasis stages. Survival analysis showed that patients with high expression of KIF23 had a poor overall survival. There were five studies in the Oncomine database in which expression of KIF23 was significantly higher in GC tissues than in normal gastric tissues ( P < 0.05). Kaplan–Meier plotter database analysis showed that recurrence-free survival, overall survival, distant metastasis free survival, and post progression survival of patients with high expression of KIF23 were lower than those of patients with low expression. Further stratified analysis found that prognostic survival indicators worsened in patients with T2 and T3 poorly differentiated adenocarcinoma with high expression of KIF23. CONCLUSION KIF23 is highly expressed in GC and is associated with a poor prognosis of patients. It may be of great significance in the diagnosis, treatment, and prognostic evaluation of GC.

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KIF26B, a novel oncogene, promotes proliferation and metastasis by activating the VEGF pathway in gastric cancer

Cited by 61 publications

References 35 publications

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation

Prognostic significance of KIF23 expression in gastric cancer

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