Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Song, Bin; Du, Juan; Song, Defeng; Ren, Jian; Feng, Yan

doi:10.1186/s40659-018-0192-5

Cited by 62 publications

(58 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[19][20][21] Several miRNAs have been identified as being associated with different cancers, including OS, 22,23 and there is evidence that miR-193b acts as a tumor suppressor in various types of cancer. [24][25][26][27][28][29][30] In the present study, we demonstrated that miR-193b expression is lower in OS specimens than in adjacent normal tissue. To better characterize the role of miR-193b, we then conducted functional studies, and showed that miR-193b overexpression induces apoptosis in OS cells, while miR-193b knockdown yields the opposite effect in vitro.…”

Section: Discussionmentioning

confidence: 78%

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

Dong¹,

Ye²,

Ma³

et al. 2019

OTT

View full text Add to dashboard Cite

Background: Osteosarcoma (OS) is one of the most common malignant bone tumors and specific microRNAs (miRNAs) are closely associated with malignant OS progression. In this study, we examined the role of and the involvement of autophagy and apoptosis in the chemosensitivity of OS cells. Methods: We employed qRT-PCR, Western blot, and immunohistochemistry to examine the expression levels of miR-193b, flap endonuclease 1 (FEN1), and autophagy-related proteins. Apoptosis was determined by flow cytometry using an Annexin V-FITC/PI apoptosis detection kit. Luciferase reporter assays confirmed the relationship between miR-193b and FEN1. Results: miR-193b was downregulated in OS compared to adjacent normal tissues (p < 0.05). miR-193b overexpression in the OS cell lines induced autophagy and apoptosis, as shown by Western blotting and flow cytometry. Knockdown of FEN1, a structure-specific nuclease overexpressed in OS tissues (p < 0.001), induced apoptosis through activation of autophagy. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-193b, FEN1 knockdown reinforced miR-193b induced apoptosis. Moreover, miR-193b expression enhanced epirubicin-induced autophagy and apoptosis. Conclusion: Collectively, the results showed that miR-193b/FEN1 may serve as a novel therapeutic target for OS aimed mainly at the induction of autophagy and apoptosis. The miR-193b/FEN1 axis increased the chemosensitivity of OS cells, while activation of autophagy enhanced the anticancer effects of epirubicin.

show abstract

Section: Discussionmentioning

confidence: 78%

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

Dong¹,

Ye²,

Ma³

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…MCPH gene overexpression is always associated with centriole overduplication, multipolar spindles, anaphase-lagging chromosomes, and micronuclei. MCPH4, MCPH7, MCPH8, MCPH10, MCPH13, MCPH17, MCPH19, and MCPH23 are highly expressed in different tumor tissues or cancer cell lines, indicating that some MCPH genes can be considered as oncogenes or potential cancer biomarkers [24][25][26][27][28][29][30][31]. The knockdown or inhibited expression of these genes may be a potential therapeutic method for cancer treatment [31][32][33].…”

Section: Some Mcph Genes Can Be Considered As Potential Cancer Biomarmentioning

confidence: 99%

“…Reduced neurons and neural progenitors, premature cell cycle exit, and increased cell death [49] N/A (Leukemia) [50] Premature neuronal differentiation [51] Nuclear division of cells (GC) [27] MCPH5 (ASPM)…”

Section: Mcph3 (Cdk5rap2)mentioning

confidence: 99%

“…The abnormal expression of MCPH4 in colorectal tumors affects cell proliferation and apoptosis [52]. In GC cells, miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of MCPH4 [27]. MCPH7 has a role to play in both primary microcephaly and cancer by its involvement in cell cycle perturbations and chromosomal segregation [61].…”

Section: Mcph Gene Regulate Neurogenesis and Carcinogenesis Through Rmentioning

confidence: 99%

“…MCPH1 (BRIT1) CHK1, CDC25, CDK1 [16] SLUG, CDK1, p53, CDH1, MDM2, SNAIL [42] p53 [110] CyclinA2, CDK2, CDC25C-cyclinB, CDC2, p53, BCL-2, Bax, Cytochrome c, Caspase-3, PARP-1 [40] MCPH2 (WDR62) JNK [18] N/A AURKA [119] PLK1 [43] MCPH3 (CDK5RAP2) p35 [120] N/A MST1, TAZ (Hippo) [121] MCPH4 (CASC5) BUB1, BUBR, ZWINT-1 [122] BUB1 [52] miR-193b-3p [27] p53 [123] MCPH5 (ASPM) The p53 gene (TP53) is classified as a tumor suppressor gene, and upregulation of its activity led to neural progenitor apoptosis in MCPH gene-deficient mice. Deletion of Mcph5 increases DNA damage and induces postnatal cerebellar progenitor apoptosis that depends on p53 [114].…”

Section: Gene Neurogenesis Ref Carcinogenesismentioning

confidence: 99%

See 2 more Smart Citations

The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis

Zhou

Zhi

et al. 2020

IJMS

View full text Add to dashboard Cite

The stem cells of neurogenesis and carcinogenesis share many properties, including proliferative rate, an extensive replicative potential, the potential to generate different cell types of a given tissue, and an ability to independently migrate to a damaged area. This is also evidenced by the common molecular principles regulating key processes associated with cell division and apoptosis. Autosomal recessive primary microcephaly (MCPH) is a neurogenic mitotic disorder that is characterized by decreased brain size and mental retardation. Until now, a total of 25 genes have been identified that are known to be associated with MCPH. The inactivation (yin) of most MCPH genes leads to neurogenesis defects, while the upregulation (yang) of some MCPH genes is associated with different kinds of carcinogenesis. Here, we try to summarize the roles of MCPH genes in these two diseases and explore the underlying mechanisms, which will help us to explore new, attractive approaches to targeting tumor cells that are resistant to the current therapies.

show abstract

Integrated analysis of patients with KEAP1/NFE2L2/CUL3 mutations in lung adenocarcinomas

et al. 2021

View full text Add to dashboard Cite

Objectives To explore the clinical features, molecular characteristics, and immune landscape of lung adenocarcinoma patients with KEAP1/NFE2L2/CUL3 mutations. Methods The multi‐omics data from the GDC‐TCGA LUAD project of The Cancer Genome Atlas (TCGA) database were downloaded from the Xena browser. The estimate of the immune infiltration was implemented by using the GSVA analysis and CIBERSORT. The status of KEAP1/NFE2L2/CUL3 mutation in 50 LUAD samples of our department was detected by using Sanger sequencing, following the relative expression level of differentially expressed genes (DEGs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was validated by IHC and real‐time quantitative polymerase chain reaction (RT‐qPCR). Results The Kaplan–Meier and multivariable Cox regression analyses demonstrated that KEAP1/NFE2L2/CUL3 mutations had independent prognostic value for OS and PFS in LUAD patients. The differential analysis detected 207 upregulated genes (like GSR/UGT1A6) and 447 downregulated genes (such as PIGR). GO, KEGG, and GSEA analyses demonstrated that DEGs were enriched in glutamate metabolism and the immune response. The constructed ceRNA network shows the linkage of differential lncRNAs and mRNAs. Three hundred and nine somatic mutations were detected, alterations in immune infiltration DNA methylations and stemness scores were also founded between the two groups. Eight mutated LUAD patients were detected by Sanger DNA sequencing in 50 surgical patients. GSR and UGT1A6 were validated to express higher in the Mut group, whereas the expression of PIGR was restrained. Furthermore, the IHC staining conducted on paraffin‐embedded tissue emphasizes the consistency of our result. Conclusion This research implemented the comprehensive analysis of KEAP1/NFE2L2/CUL3 somatic mutations in the LUAD patients. Compared with the wild type of LUAD patients, the Mut group shows a large difference in clinical features, RNA sequence, DNA methylation, and immune infiltrations, indicating complex mechanism oncogenesis and also reveals potential therapeutic targets.

show abstract

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

Cited by 62 publications

References 43 publications

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

<p>miR-193b Increases the Chemosensitivity of Osteosarcoma Cells by Promoting FEN1-Mediated Autophagy</p>

The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis

Integrated analysis of patients with KEAP1/NFE2L2/CUL3 mutations in lung adenocarcinomas

Contact Info

Product

Resources

About