Aberrant KIF23 expression is associated with adverse clinical outcome and promotes cellular malignant behavior through the Wnt/β-catenin signaling pathway in Colorectal Cancer

et al. 2022

Preprint

Background: Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. MKLP1 plays a crucial role in tumorigenesis and cancer progression. However, the role of MKLP1 in triple negative breast cancer and the underlying mechanism remain unknown. The study aimed to elucidate the biological function regulatory mechanism of MKLP1 in triple negative breast cancerMethods: Quantitative real-time PCR and Western blotting were used to determine the MKLP1 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of MKLP1 on tumor growth and metastasis in triple negative breast cancer. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of MKLP1 in triple negative breast cancer.Results: We found that MKLP1 was significantly up-regulated and associated with poor prognosis in triple negative breast cancer. MKLP1 could promote triple negative breast cancer proliferation, migration and invasion in vitro and in vivo. MKLP1 could activate Wnt/β-catenin pathway and promote EMT progression. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of MKLP1 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression. Conclusions: Our findings elucidate WDR5/FOXM1/MKLP1/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 95%

Mitotic kinesin-like protein 1, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/β-catenin pathway

Yang

et al. 2022

Preprint

“…In our study, we found KIF23 was upregulated in TNBC and associated with prognosis of TNBC by bioinformatic analysis. Several studies showed KIF23 plays an oncogenic role in several cancer types [ 13 , 49 ]. Moreover, our results illustrated KIF23 was upregulated in TNBC cell lines and tissues.…”

Section: Discussionmentioning

confidence: 99%

“…And aberrant Wnt signaling pathway was associated with tumor proliferation, metastasis, stemness and drug resistance [ 25 , 26 , 55 , 56 ]. It was reported KIF23 could activate Wnt/β-catenin signaling pathway in gastric and colorectal cancer [ 13 , 49 ], and then we explored whether KIF23 affected Wnt/β-catenin signaling pathway in TNBC. Our results showed the related genes of Wnt/β-catenin signaling pathway, such as β-catenin, CyclinD1 and c-myc, were upregulated due to the KIF23 overexpression, indicating KIF23 promotes TNBC progression via activating this pathway.…”

Section: Discussionmentioning

confidence: 99%

Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/β-catenin pathway

Yang

et al. 2022

J Exp Clin Cancer Res

Background Triple negative breast cancer (TNBC) is highly malignant and has a worse prognosis, compared with other subtypes of breast cancer due to the absence of therapeutic targets. KIF23 plays a crucial role in the tumorigenesis and cancer progression. However, the role of KIF23 in development of TNBC and the underlying mechanism remain unknown. The study aimed to elucidate the biological function and regulatory mechanism of KIF23 in TNBC. Methods Quantitative real-time PCR and Western blot were used to determine the KIF23 expression in breast cancer tissues and cell lines. Then, functional experiments in vitro and in vivo were performed to investigate the effects of KIF23 on tumor growth and metastasis in TNBC. Chromatin immunoprecipitation assay was conducted to illustrate the potential regulatory mechanisms of KIF23 in TNBC. Results We found that KIF23 was significantly up-regulated and associated with poor prognosis in TNBC. KIF23 could promote TNBC proliferation, migration and invasion in vitro and in vivo. KIF23 could activate Wnt/β-catenin pathway and promote EMT progression in TNBC. In addition, FOXM1, upregulated by WDR5 via H3K4me3 modification, directly bound to the promoter of KIF23 gene to promote its transcription and accelerated TNBC progression via Wnt/β-catenin pathway. Both of small inhibitor of FOXM1 and WDR5 could inhibit TNBC progression. Conclusions Our findings elucidate WDR5/FOXM1/KIF23/Wnt/β-catenin axis is associated with TNBC progression and may provide a novel and promising therapeutic target for TNBC treatment.

“…KIF18A and KIF23 are members of the kinesin superfamily of microtubule-associated molecular motors, which are related to chromosome separation, intracellular transport, mitotic spindle formation and cytokinesis. Aberrant expressions of KIF18A and KIF23 were related to metastasis and poor prognosis in colorectal cancer [98,99]. TTK could regulate tumor proliferation and differentiation and predict prognosis in colon cancer [100].…”

Section: Discussionmentioning

confidence: 99%

Weighted Gene Coexpression Network Analysis of Key Genes Controlling Cancer Stem Cell Characteristics by Mrnasi in Colon Adenocarcinoma

Yin

Tong

2021

Preprint

Background: Cancer stem cells are hidden tumor cells with the potential for self-renewal and multi-differentiation, which are the principal cause of tumor heterogeneity, metastasis and drug resistance. However, the key genes that maintain cell stemness of colon adenocarcinoma (COAD) are still unknown. Our study was designed to identify key genes associated with the stemness of COAD cell. Methods: RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Weighted gene coexpression network analysis (WGCNA) was used to recognize key genes based on mRNAsi. Next, the gene expression data downloaded from Gene Expression Omnibus (GEO), Oncomine, and Gene Expression Profiling Integrative Analysis (GEPIA) were used to demonstrate the expression of key genes.Results: The mRNAsi score of COAD tissue was obviously superior than that of normal tissue. N stages, M stages and overall survival were highly related to mRNAsi. WGCNA showed that the green module was positively related to mRNAsi. We obtained 27 genes closely related to each other at the transcriptional and protein levels. The main biological functions of key genes were organelle fission, chromosomal region, and protein serine/threonine kinase activity. The enriched signaling pathway were cell cycle, progesterone−mediated oocyte maturation, human T−cell leukemia virus 1 infection, oocyte meiosis, DNA replication, cellular senescence, viral carcinogenesis, and p53 signaling pathway. The key genes were highly expressed in COAD and various cancers, which was validated multiple databases. Conclusions: 27 key genes were well correlated with maintaining stemness of COAD, which were significantly related to cell cycle events. The key genes may be therapeutic targets for inhibiting the properties of COAD stem cells.