LncRNA ARAP1-AS1 Promotes Bladder Cancer Development by Regulating the miR-3918/KIF20A Axis

Zhang, Wei; Zhang, Jingyu; Zhang, Hu; Sun, Wei; Xu, Lv; Chu, Hao; Wang, Xiao; Fu, Qiao

doi:10.1007/s12033-022-00489-x

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…CCNE2 was a downstream gene of miR‐3607‐3p to participate in cell growth and metastasis in NSCLC cells (P. Gao et al, 2018). Additional research about KIF20A indicated that KIF20A regulated by miR‐3918 contributed to the malignant cell behaviors in bladder cancer (W. Zhang et al, 2022). Furthermore, recent research revealed that KIF2A might be a prognostic marker and therapeutic target of NSCLC (F. Xie et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Wang

Hua

et al. 2023

Drug Development Research

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BackgroundNonsmall cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85%. Berberine (BBR), a commonly used traditional Chinese medicine, has been reported to exhibit a potential antitumor effect in various cancers. In this research, we explored the function of BBR and its underlying mechanisms in the development of NSCLC.MethodsCell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐20‐deoxyuridine (EdU), colony formation assays, flow cytometry, and transwell invasion assay were employed to determine cell growth, the apoptotic rate, cell invasion of NSCLC cells, respectively. Western blot was applied for detecting the protein expression of c‐Myc, matrix metalloprotease 9 (MMP9), kinesin family member 20A (KIF20A), cyclin E2 (CCNE2), and phosphatidylinositol‐3‐kinase/protein kinase B (PI3K/AKT) pathway‐related proteins. Glycolysis was evaluated by detecting glucose consumption, lactate production, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio with the matched kits. Real‐time quantitative polymerase chain reaction (RT‐qPCR) was conducted to analyze the level of KIF20A and CCNE2. Tumor model was established to evaluate the function of BBR on tumor growth in NSCLC in vivo. In addition, immunohistochemistry assay was employed to detect the level of KIF20A, CCNE2, c‐Myc, and MMP9 in mice tissues.ResultsBBR exhibited suppressive effects on the progression of NSCLC, as evidenced by inhibiting cell growth, invasion, glycolysis, and facilitating cell apoptosis in H1299 and A549 cells. KIF20A and CCNE2 were upregulated in NSCLC tissues and cells. Moreover, BBR treatment significantly decreased the expression of KIF20A and CCNE2. KIF20A or CCNE2 downregulation could repress cell proliferation, invasion, glycolysis, and induce cell apoptosis in both H1299 and A549 cells. The inhibition effects of BBR treatment on cell proliferation, invasion, glycolysis, and promotion effect on cell apoptosis were rescued by KIF20A or CCNE2 overexpression in NSCLC cells. The inactivation of PI3K/AKT pathway caused by BBR treatment in H1299 and A549 cells was restored by KIF20A or CCNE2 upregulation. In vivo experiments also demonstrated that BBR treatment could repress tumor growth by regulating KIF20A and CCNE2 and inactivating the PI3K/AKT pathway.ConclusionBBR treatment showed the suppressive impact on the progression of NSCLC by targeting KIF20A and CCNE2, thereby inhibiting the activation of the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Wang

Hua

et al. 2023

Drug Development Research

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“…[ 35 , 36 ] There is evidence that KIF20A linked to cancer. [ 37 , 38 ] Related studies have shown that ARAP1-AS1 regulates expression of KIF20A by infiltrating miR-3918, thereby helping bladder cancer cells activity, [ 39 ] affecting survival level of bladder cancer. [ 16 ] KIF20A is also responsible for intracellular trafficking of vesicles and organelles, and cell mitotic spindle formation.…”

Section: Discussionmentioning

confidence: 99%

High expression of KIF20A in bladder cancer as a potential prognostic target for poor survival of renal cell carcinoma

Liu

Fan

et al. 2023

Medicine

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Urinary system tumors are malignant tumors, including renal cancer and bladder cancer. however, molecular target of them remains unclear. GSE14762 and GSE53757 were downloaded from GEO database to screen differentially expressed genes (DEGs). Weighted gene co-expression network analysis was performed. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes were used for enrichment analysis. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were performed on whole genome, as formulated by gene set enrichment analysis. Survival analysis was also performed. Comparative toxicogenomics database was used to identify diseases most associated with hub genes. A total of 1517 DEGs were identified. DEGs were mainly enriched in cancer pathway, HIF-1 signaling pathway, organic acid metabolism, glyoxylate and dicarboxylate metabolism, and protein homodimerization activity. Ten hub genes (TPX2, ASPM, NUSAP1, RAD51AP1, CCNA2, TTK, PBK, MELK, DTL, kinesin family member 20A [KIF20A]) were obtained, which were up-regulated in tumor tissue. The expression of KIF20A was related with the overall survival of renal and bladder cancer. KIF20A was up-regulated in the tumor tissue, and might worsen the overall survival of bladder and kidney cancer. KIF20A could be a novel biomarker of bladder and kidney cancer.

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“…KIF20A is overexpressed in many types of cancer cells, including breast, lung, liver, pancreatic, ovarian, and colorectal cancers, as well as bladder and renal cancers, as we discussed earlier [ 31 ]. Overexpression of KIF20A has been associated with aggressive behavior and poor prognosis in cancer patients, and inhibiting KIF20A expression has been shown to reduce cancer cell proliferation and induce cell death in vitro and in animal models [ 32 ]. Moreover, studies have shown that KIF20A interacts with other proteins involved in cell cycle regulation and cancer development, such as Aurora-A and PLK1, suggesting that KIF20A may play a crucial role in the regulation of cell division and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

KIF20A as a potential biomarker of renal and bladder cancers based on bioinformatics and experimental verification

Wang

et al. 2023

Aging

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Background: Bladder cancer (BC) is a malignant tumor that occurs in the bladder wall and often appears in elderly individuals. Renal cancer (RC) arises from the renal tubular epithelium, but its molecular mechanism remains unclear. Methods: We downloaded RC datasets (GSE14762 and GSE53757) and a BC dataset (GSE121711) to screen differentially expressed genes (DEGs). We also performed weighted gene coexpression network analysis (WGCNA). We created a protein-protein interaction (PPI) network and performed functional enrichment analysis, such as gene set enrichment analysis (GSEA). Heatmaps were made for gene expression. Survival analysis and immunoinfiltration analysis were performed. Comparative toxicogenomics database (CTD) analysis was performed to find the relationship between disease and hub genes. Western blotting was performed to verify the role of KIF20A in apoptosis. Results: A total of 764 DEGs were identified. The GSEA showed that the DEGs were mainly enriched in organic acid metabolism, drug metabolism, mitochondria, and metabolism of cysteine and methionine. The PPI network in GSE121711 showed that KIF20A was a hub gene of renal clear cell carcinoma. Where the expression level of KIF20A was higher, the prognosis of patients was worse. CTD analysis showed that KIF20A was associated with inflammation, proliferation, and apoptosis. KIF20A expression in the RC group was upregulated, as shown by western blotting. The core proteins (including pRB Ser 780, CyclinA, E2F1, CCNE1, and CCNE2) in the pRB Ser 780/CyclinA signaling pathway were also upregulated in the RC group. Conclusions: KIF20A might be a novel biomarker for researching renal and bladder cancers.

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LncRNA ARAP1-AS1 Promotes Bladder Cancer Development by Regulating the miR-3918/KIF20A Axis

Cited by 8 publications

References 21 publications

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway

High expression of KIF20A in bladder cancer as a potential prognostic target for poor survival of renal cell carcinoma

KIF20A as a potential biomarker of renal and bladder cancers based on bioinformatics and experimental verification

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