Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

Li, Gang; Chong, Tie; Yang, Jie; Li, Hongliang; Chen, Haiwen

doi:10.3727/096504018x15213115046567

Cited by 30 publications

(35 citation statements)

References 41 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Findings were validated using BC fresh tissues and paraffin‐embedded specimens from our center. Results showed that KIFC1 was upregulated at both the mRNA and protein levels in BC tissues, consistent with the expression pattern of KIFC1 in other reported tumors . We investigated the relationship between KIFC1 expression and the clinicopathological features of patients with BC who had undergone radical cystectomy by performing IHC on 152 BC specimens.…”

Section: Discussionsupporting

confidence: 77%

“…KIFC1, which plays an important role in the bipolar mitotic division of cancer cells, is greatly significant in maintaining cancer cell survival, but is redundant in normal cells . KIFC1 had been reported to drive tumor proliferation, metastasis, and drug resistance in several cancers, and is related to shorter overall survival rate and poor prognosis, suggesting that KIFC1 might be a promising therapeutic target. However, the relationship between KIFC1 expression and prognosis of BC remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, KIFC1 was able to induce drug resistance against taxane in prostate cancer, tamoxifen, and docetaxel in breast cancer . Furthermore, upregulation of KIFC1 has been identified in several solid human cancers including esophageal squamous cell carcinoma, gastric cancer, and renal cell carcinoma . These data, together, suggested that KIFC1 plays a crucial oncogenic role in tumorigenesis.…”

Section: Introductionmentioning

confidence: 92%

See 2 more Smart Citations

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial–mesenchymal transition via Akt/GSK3β signaling

Xiao

Teng

et al. 2019

Cancer Science

View full text Add to dashboard Cite

Kinesin family member C1 (KIFC1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC1 in bladder cancer (BC) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real‐time PCR and western blotting assays. All data showed that KIFC1 was significantly upregulated in BC specimens at both the mRNA and protein levels. Immunohistochemical studies in a cohort of 152 paraffin‐embedded BC tissues displayed that upregulated expression of KIFC1 clearly correlated with pT status (P = .014) and recurrent status (P = .002). Kaplan‐Meier survival analysis and log‐rank test indicated that patients with BC with high KIFC1 expression had both shorter cancer‐specific survival (P < .001) and recurrence‐free survival time (P < .001) than those with low KIFC1 expression. Furthermore, ectopic downregulation of KIFC1 weakened BC cell proliferation and migration both in vitro and in vivo, whereas upregulation of KIFC1 enhanced this in vitro. Overexpression of KIFC1 phosphorylated GSK3β and promoted Snail through activating AKT (protein kinase B0) to induce proliferation and epithelial–mesenchymal transition (EMT) and, therefore, substantially promoted BC migration and metastasis. Our study revealed an oncogenic role for KIFC1 to promote BC cell proliferation and EMT via Akt/GSK3β signaling; KIFC1 might be a promising prognostic biomarker as well as a therapeutic target for BC.

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial–mesenchymal transition via Akt/GSK3β signaling

Xiao

Teng

et al. 2019

Cancer Science

View full text Add to dashboard Cite

show abstract

“…Among 26 downstream genes, several genes have already reported roles in RCC pathogenesis. ITGA4 promoted cancer cell metastasis and the kinesin family was related to cell proliferation, invasion, and migration in RCC . Interestingly, high expression of 7 genes ( SDC3 , PLXDC1 , IL18RAP , GZMH , ATP8B3 , TBX15 , and TMC8 ) significantly predicted poor prognosis of RCC patients according to TCGA datasets.…”

Section: Discussionmentioning

confidence: 99%

“…ITGA4 promoted cancer cell metastasis and the kinesin family was related to cell proliferation, invasion, and migration in RCC. 36,37 Interestingly, high expression of 7 genes (SDC3, PLXDC1, IL18RAP, GZMH, ATP8B3, TBX15, and TMC8) significantly predicted poor prognosis of RCC patients according to TCGA datasets. PLXDC1 (also known as TEM7) was initially cloned as a high expression protein from vascular endothelium of human cancer.…”

mentioning

confidence: 99%

Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance

et al. 2018

View full text Add to dashboard Cite

In the human genome, miR‐451a, miR‐144‐5p (passenger strand), and miR‐144‐3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR‐451a: P = .00305; miR‐144‐5p: P = .00128; miR‐144‐3p: P = 9.45 × 10−5). We previously reported that miR‐451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR‐144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR‐144‐5p and miR‐144‐3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR‐144‐5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2,TRIP13,ANKRD36,CENPF,NCAPG,CLEC2D,SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR‐144‐5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP,SDC3,SH2D1A,GZMH,KIF21B,TMC8,GAB3,HLA‐DPB2,PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR‐144‐5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR‐451a, miR‐144‐5p, and miR‐144‐3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis.

show abstract

Target‐based virtual screening, computational multiscoring docking and molecular dynamics simulation of small molecules as promising drug candidate affecting kinesin‐like protein KIFC1

Khan

Ahmad

Rabbani³

et al. 2022

Cell Biochemistry & Function

View full text Add to dashboard Cite

The kinesin family member C1 (KIFC1) is an essential protein that facilitates the bipolar division of neoplastic cells. Inhibiting KIFC1 by small molecules is a lucrative strategy to impede bipolar mitosis leading to the apoptosis of cancerous cells. The research aims to envisage small‐molecule inhibitors targeting KIFC1. The Mcule database, a comprehensive online digital platform containing more than five million chemical compounds, was used for structure‐based virtual screening (SBVS). Druglikeness filtration sifted 2,293,282 chemical hits that further narrowed down to 49 molecules after toxicity profiling. Finally, 39 compounds that comply with the BOILED‐Egg permeation predictive model of the ADME rules were carried forward for multiscoring docking using the AutoDock Vina inbuilt to Mcule drug discovery platform, DockThor and SwissDock tools. The mean of ΔG terms produced by docking tools was computed to find consensus top ligand hits. AZ82 exhibited stronger binding (Consensus ΔG: −7.99 kcal mol−1) with KIFC1 among reference inhibitors, for example, CW069 (−7.57 kcal mol−1) and SR31527 (−7.01 kcal mol−1). Ten ligand hits namely, Mcule‐4895338547 (Consensus ΔG: −8.69 kcal mol−1), Mcule‐7035674888 (−8.42 kcal mol−1), Mcule‐5531166845 (−8.53 kcal mol−1), Mcule‐3248415882 (−8.55 kcal mol−1), Mcule‐291881733 (−8.41 kcal mol−1), Mcule‐5918624394 (−8.44), Mcule‐3470115427 (−8.47), Mcule‐3686193135 (−8.18 kcal mol−1), Mcule‐3955355291 (8.09 kcal mol−1) and Mcule‐9534899193 (−8.01 kcal mol−1) depicted strong binding interactions with KIFC1 in comparison to potential reference inhibitor AZ82. The top four ligands and AZ82 were considered for molecular dynamics simulation of 50 ns duration. Toxicity profiling, physicochemical properties, lipophilicity, solubility, pharmacokinetics, druglikeness, medicinal chemistry attributes, average potential energy, RMSD, RMSF, SASA, ΔGsolv and Rg analyses forecast the ligand mcule‐4895338547 as a promising inhibitor of KIFC1.

show abstract

Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

Cited by 30 publications

References 41 publications

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial–mesenchymal transition via Akt/GSK3β signaling

Kinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial–mesenchymal transition via Akt/GSK3β signaling

Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance

Target‐based virtual screening, computational multiscoring docking and molecular dynamics simulation of small molecules as promising drug candidate affecting kinesin‐like protein KIFC1

Contact Info

Product

Resources

About