Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-β signaling

Wang, Chengqin; Wang, Chenggang; Wei, Zhimin; Li, Yujun; Wang, Wenhong; Li, Xia; Zhao, Jing; Zhou, Xuan; Qu, Xun; Xiang, Fenggang

doi:10.1016/j.canlet.2015.07.037

Cited by 35 publications

(34 citation statements)

References 41 publications

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“…On the other hand, it can promote genetic and epigenetic alterations, change cellular metabolism, directly and indirectly control inflammation, cancer cell proliferation and survival, epithelial-to-mesenchymal transition (EMT), invasion, angiogenesis and metastasis (44). Common genes also include kinesins, the misregulation of which are involved in cancer pathogenesis, such as uncontrolled cell growth and metastasis (45,46). At the same time, a group of growth factors are also involved in this chromosome structure changes and the relationship between them and how they contribute to cancer initiation and development remains to be further investigated.…”

Section: General Architecture Of Chromatin In Cancer Cellmentioning

confidence: 99%

Domain segregated 3D chromatin structure and segmented DNA methylation in carcinogenesis

Xue

Yang

Tian

et al. 2020

Preprint

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The three-dimensional (3D) chromatin structure, together with DNA methylation and other epigenetic marks, profoundly affects gene expression and displays abnormal behaviors in cancer cells. We elucidated the chromatin architecture remodeling in carcinogenesis from the perspective of spatial interactions between CGI forest and prairie domains, which are two types of megabase-sized domains defined by different sequence features but show distinct epigenetic and transcriptional patterns. DNA sequence strongly affects chromosome spatial interaction, DNA methylation and gene expression. Globally, forests and prairies show enhanced spatial segregation in cancer cells and such structural changes are accordant with the alteration of CGI interactions and domain boundary insulation, which could affect vital cancer-related properties. As the cancer progresses, a gradual increase of the DNA methylation difference between the two types of DNA domains is also observed for many different types of cancers. These observations are consistent with the change of transcriptional level differences of genes in these two domains, suggesting a highly-connected global structural, epigenetic and transcriptional activity changes in carcinogenesis.3 development and its relationship with chromosomal structural changes remain largely unknown.In principle, both chromosomal structure and epigenetic modifications can influence gene expression. Based on Hi-C contact map, the chromatin is divided into compartments A and B (2).Genes are enriched in compartment A and their expression levels are higher than those in compartment B. But there are many questions remain unanswered, e.g. what factors determine the compartment formation, what are the driving forces of compartment switch, and what are the roles of compartmentalization in cancer? Our previous study (25) showed that the compartment formation is strongly related to the genome composition. Based on the uneven distribution of CGIs, the whole genome was divided into two types of megabase-sized domains, CGI-rich domains (named as CGI forest domains) and CGI-poor domains (named as CGI prairie domains).These two types of domains, differing in sequence features, show distinct epigenetic and transcriptional patterns and overlap strongly with the compartments A and B, respectively. Furthermore, the cell-specific spatial contact and separation between these two types of domains are strongly coupled with various biological processes, such as early embryonic development (26), cell differentiation, and senescence (27). The main goal of this study is to understand the sequence dependence of various carcinogenesis marks and we found that forest and prairie behave significantly differently, including their distribution in compartments, CGI interactions, TAD formation, gene expression and epigenetic marks, especially DNA methylation, which is closely associated with development stage of cancer. The property difference between forest and prairie enlarges in cancer, consistent with their increased spatial separati...

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Section: General Architecture Of Chromatin In Cancer Cellmentioning

confidence: 99%

Domain segregated 3D chromatin structure and segmented DNA methylation in carcinogenesis

Xue

Yang

Tian

et al. 2020

Preprint

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“…Low levels of EPHA4 and OVOL2 have been associated with poor survival and epithelial-to-mesenchymal transition (EMT), respectively, in lung adenocarcinoma (19,20). On the other hand, increased expressions of LOXL2, AXL, and CDH2 have been associated with poor prognosis in lung cancer (21)(22)(23), whereas high levels of the kinesin family members KIF3C and KIF20A were associated with lymph node metastasis in breast cancer and with poor overall survival in cervical squamous cell carcinoma, respectively (24,25). qRT-PCR analyses confirmed downregulation of OVOL2 and EPHA4 and upregulation of LOXL2, AXL, CDH2, KIF3C, and KIF20A in the CRISPRa-14q32 cells (Fig.…”

Section: Modulation Of Genes Involved In Cell Motility Processes Explmentioning

confidence: 99%

“…In this regard, miRNAs are promising cancer biomarkers and represent target molecules for the development of new antitumor therapies. miRNAs are noncoding RNAs consisting of [19][20][21][22][23][24][25] nucleotides that affect gene expression posttranscriptionally through the physical interaction with specific RNA transcripts (targets) leading to translational inhibition or degradation (2). Several studies have shown that miRNAs target oncogenes and tumor suppressor genes and, thus, are actively involved in regulating cancer hallmarks, such as proliferation, invasion, and metastasis (3).…”

Section: Introductionmentioning

confidence: 99%

Epigenetically Regulated Chromosome 14q32 miRNA Cluster Induces Metastasis and Predicts Poor Prognosis in Lung Adenocarcinoma Patients

González-Vallinas

Rodríguez-Paredes

Albrecht

et al. 2018

Molecular Cancer Research

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Most lung cancer deaths are related to metastases, which indicates the necessity of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify miRNAs involved in metastasis of lung adenocarcinoma as prognostic biomarkers and therapeutic targets. To that end, lymph node metastasis-associated miRNAs were identified in The Cancer Genome Atlas lung adenocarcinoma patient cohort (sequencing data; = 449) and subsequently validated by qRT-PCR in an independent clinical cohort ( = 108). Overexpression of miRNAs located on chromosome 14q32 was associated with metastasis in lung adenocarcinoma patients. Importantly, Kaplan-Meier analysis and log-rank test revealed that higher expression levels of individual 14q32 miRNAs (mir-539, mir-323b, and mir-487a) associated with worse disease-free survival of never-smoker patients. Epigenetic analysis including DNA methylation microarray data and bisulfite sequencing validation demonstrated that the induction of 14q32 cluster correlated with genomic hypomethylation of the 14q32 locus. CRISPR activation technology, applied for the first time to functionally study the increase of clustered miRNA levels in a coordinated manner, showed that simultaneous overexpression of 14q32 miRNAs promoted tumor cell migratory and invasive properties. Analysis of individual miRNAs by mimic transfection further illustrated that miR-323b-3p, miR-487a-3p, and miR-539-5p significantly contributed to the invasive phenotype through the indirect regulation of different target genes. In conclusion, overexpression of 14q32 miRNAs, associated with the respective genomic hypomethylation, promotes metastasis and correlates with poor patient prognosis in lung adenocarcinoma. This study points to chromosome 14q32 miRNAs as promising targets to inhibit tumor cell dissemination and to predict patient prognosis in lung adenocarcinoma. .

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“…In contrast, TGF-β also exerts tumor-suppressive effects. In other words, the output of the TGF-β signaling pathway depends on the stage of tumor development and type of tumor tissue [73]. Numerous studies have confirmed a close relationship between HBx and TGF-β.…”

Section: Hepatitis B Virus X Protein and Components Of The Liver Tumomentioning

confidence: 99%

Hepatitis B virus X protein in liver tumor microenvironment

Zhou

et al. 2016

Tumor Biol.

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Encoded by the hepatitis B virus, hepatitis B virus X protein (HBx) is a multifunctional, potentially oncogenic protein that acts primarily during the progression from chronic hepatitis B to cirrhosis and hepatocellular carcinoma (HCC). In recent decades, it has been established that chronic inflammation generates a tumor-supporting microenvironment. HCC is a typical chronic inflammation-related cancer, and inflammation is the main risk factor for HCC progression. The viral transactivator HBx plays a pivotal role in the initiation and maintenance of hepatic inflammatory processes through interactions with components of the tumor microenvironment including tumor cells and the surrounding peritumoral stroma. The complex interactions between HBx and this microenvironment are thought to regulate tumor growth, progression, invasion, metastasis, and angiogenesis. In this review, we have summarized the current evidence evaluating the function of HBx and its contribution to the inflammatory liver tumor microenvironment.

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Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-β signaling

Cited by 35 publications

References 41 publications

Domain segregated 3D chromatin structure and segmented DNA methylation in carcinogenesis

Domain segregated 3D chromatin structure and segmented DNA methylation in carcinogenesis

Epigenetically Regulated Chromosome 14q32 miRNA Cluster Induces Metastasis and Predicts Poor Prognosis in Lung Adenocarcinoma Patients

Hepatitis B virus X protein in liver tumor microenvironment

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