Identification of Novel Molecular Therapeutic Targets and Their Potential Prognostic Biomarkers Among Kinesin Superfamily of Proteins in Pancreatic Ductal Adenocarcinoma

Yang, Yang; Gao, Lanyang; Weng, Ningna; Li, Junjun; Liu, Jin Lu; Zhou, Ying; Long, Rong; Xiong, Qunli; Xu, Yongfeng; Varela-Ramı́rez, Armando; Zhu, Qing

doi:10.3389/fonc.2021.708900

Cited by 9 publications

(8 citation statements)

References 51 publications

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“…Low KIF21B expression indirectly increased the apoptosis and inhibited the proliferation of osteosarcoma cells [ 40 ]. A recent study by Yang et al [ 41 ] also indicated that the overexpression of KIF21B was associated with the immunological and oncogenic pathway activation in pancreatic cancer. Herein, our data highlighted the oncogenic role of KIF21B in GC.…”

Section: Discussionmentioning

confidence: 99%

Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer

et al. 2022

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Recently, kinesin family member 21B (KIF21B) has been reported to be an oncogene in non-small cell lung cancer and hepatocellular carcinoma. However, the functional role of KIF21B and related molecular mechanisms in gastric cancer (GC) remain largely uncovered. In this study, online bioinformatics analysis showed that KIF21B was overexpression in GC and predicted poor prognosis. Consistently, we found that the protein expression of KIF21B was upregulated in GC tissues compared with adjacent tissues by immunohistochemistry. Knockdown of KIF21B significantly suppressed cell proliferation, migration and invasion in GC cell lines (AGS and SNU-5) using Cell counting kit‑8 (CCK-8) assay, colony formation and transwell assay. KIF21B was confirmed as the target of miR-132-3p in GC cells by luciferase reporter assay. Moreover, miR-132-3p was down-regulated and KIF21B expression was upregulated in GC tissues. Overexpression of KIF21B reversed the miR-132-3p-mediated suppressive effects on GC cell proliferation, migration and invasion. Furthermore, miR-132-3p overexpression downregulated the protein levels of Wnt1, c-Myc, β-catenin, proliferating cell nuclear antigen (PCNA) and N-cadherin, and upregulated E-cadherin expression in GC cells, which were all alleviated after KIF21B overexpression. In conclusion, our findings indicate that down-regulation of KIF21B by miR-132-3p suppresses cellular functions in GC, which might be linked to reduced Wnt/β-catenin signaling.

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Section: Discussionmentioning

confidence: 99%

Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer

et al. 2022

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“…The kinesin superfamily (KIFs), known as molecular motors with microtubule (MT) class-binding protein superfamily, play pivotal roles in several biological processes, including axonal transport and microtubule stabilization in our body, especially in the brain, that are important for various highly aggressive malignancies including glioma [ 22 ]. Although several compounds targeting mitotic kinesins, including the taxanes, vinca alkaloids, and epothilones, have been successfully used in the treatment of a number of hematologic and solid malignancies, the same efficacy does not appear in glioma patients [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Gene Signature Based on Kinesin Family Members to Predict Prognosis in Glioma

Pan

Fang

2023

Medicina

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Background and Objectives: Extensive research indicates that the kinesin superfamily (KIFs) regulates tumor progression. Nonetheless, the potential prognostic and therapeutic role of KIFs in glioma has been limited. Materials and Methods: Four independent cohorts from The Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA) database were generated into a large combination cohort for identification of the prognostic signature. Following that, systematic analyses of multi-omics data were performed to determine the differences between the two groups. In addition, IDH1 was selected for the differential expression analysis. Results: The signature consists of five KIFs (KIF4A, KIF26A, KIF1A, KIF13A, and KIF13B) that were successfully identified. Receiver operating characteristic (ROC) curves indicated the signature had a suitable performance in prognosis prediction with the promising predictive area under the ROC curve (AUC) values. We then explored the genomic features differences, including immune features and tumor mutation status between high- and low-risk groups, from which we found that patients in the high-risk group had a higher level of immune checkpoint modules, and IDH1 was identified mutated more frequently in the low-risk group. Results of gene set enrichment analysis (GSEA) analysis showed that the E2F target, mitotic spindle, EMT, G2M checkpoint, and TNFa signaling were significantly activated in high-risk patients, partially explaining the differential prognosis between the two groups. Moreover, we also verified the five signature genes in the Human Protein Atlas (HPA) database. Conclusion: According to this study, we were able to classify glioma patients based on KIFs in a novel way. More importantly, the discovered KIFs-based signature and related characteristics may serve as a candidate for stratification indicators in the future for gliomas.

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“…In this study, KRAS mutation was related to decreased expression of KIF4A in LUAD. In contrast, an analysis of cBioPortal data revealed that KIF4A was upregulated in KRAS -mutant pancreatic ductal adenocarcinoma patient tissues [ 66 ]. It is possible that KRAS might regulate KIF4A in a cell type-specific manner, and this particular regulation in the context of lung cancer requires further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer

Singharajkomron

Yodsurang

Seephan

et al. 2022

IJMS

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Microtubule-associated proteins (MAPs) play essential roles in cancer development. This study aimed to identify transcriptomic biomarkers among MAP genes for the diagnosis and prognosis of lung cancer by analyzing differential gene expressions and correlations with tumor progression. Gene expression data of patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) from the Cancer Genome Atlas (TCGA) database were used to identify differentially expressed MAP genes (DEMGs). Their prognostic value was evaluated by Kaplan–Meier and Cox regression analysis. Moreover, the relationships between alterations in lung cancer hallmark genes and the expression levels of DEMGs were investigated. The candidate biomarker genes were validated using three independent datasets from the Gene Expression Omnibus (GEO) database and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on clinical samples. A total of 88 DEMGs were identified from TCGA data. The 20 that showed the highest differential expression were subjected to association analysis with hallmark genes. Genetic alterations in TP53, EGFR, PTEN, NTRK1, and PIK3CA correlated with the expression of most of these DEMGs. Of these, six candidates—NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2—were significantly differentially expressed and correlated with the overall survival (OS) of the patients. The mRNA expression profiles of these candidates were consistently verified using three GEO datasets and qRT-PCR on patient lung tissues. The expression levels of NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2 can serve as diagnostic biomarkers for LUAD and LUSC. Moreover, the first five can serve as prognostic biomarkers for LUAD, while LRRK2 can be a prognostic biomarker for LUSC. Our research describes the novel role and potential application of MAP-encoding genes in clinical practice.

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Identification of Novel Molecular Therapeutic Targets and Their Potential Prognostic Biomarkers Among Kinesin Superfamily of Proteins in Pancreatic Ductal Adenocarcinoma

Cited by 9 publications

References 51 publications

Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer

Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer

Identification of a Novel Gene Signature Based on Kinesin Family Members to Predict Prognosis in Glioma

Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer

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