miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling

Huang, Xiangjie; Xiao, Sisi; Zhu, Xinping; Yu, Yun; Cao, Meng; Zhang, Xiaodong; Li, Shaotang; Zhu, Wenxiu; Wu, Feifei; Zheng, Xiaohui; Jin, Libo; Xie, Congying; Huang, Xiaoying; Zou, Peng; Li, Xiaokun; Cui, Ri

doi:10.1038/s41419-020-02997-7

Cited by 28 publications

(31 citation statements)

References 44 publications

(61 reference statements)

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“…FN1 is related to TNM staging, lymph node metastasis and OS and promotes the metastasis of GC cell lines [12]. IL-6-mediated signal transducer and activator of transcription 3 (STAT3) activation can promote the tumorigenesis of non-small-cell lung cancer through the activating NF-κB pathway [16]. The overexpression of POSTN in tumors is an indicator of poor prognosis in colorectal cancer [8].…”

Section: Discussionmentioning

confidence: 99%

Construction of Prognostic Prediction Model for Stomach Adenocarcinoma Based on the TCGA Database.

Gu¹,

Chen²,

Wang³

2020

Preprint

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Background: Prognostic prediction models have been developed to detect new biomarkers of gastric cancer (GC). The identification of new biomarkers could provide theoretical foundations for the application of molecular targeted therapy in advanced GC. The aim of this study was to construct a prognostic prediction model for stomach adenocarcinoma (STAD) based on The Cancer Genome Atlas (TCGA) database. Methods: First, we used the "limma" package to screen differentially expressed genes (DEGs) based on TCGA database. Gene ontology (GO) analysis was performed using the "ClusterProfiler" package. The interactions between proteins and the relationships between differentially expressed genes and clinical features were analyzed by protein-protein interaction (PPI) network analysis and weighted gene coexpression network analysis (WGCNA), respectively. Then, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to identify differentially enriched pathways. The GenVisR package and CIBERSORT were used to identify mutations and assess immune infiltration. Finally, the expression of COL3A1 in STAD tissues was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting.Results: Six differentially expressed genes were screened out, namely, COL3A1, ADAMTS12, BGN, FNDC1, AEBP1 and HTRA3. The enrichment results showed that differentially expressed genes were involved in multiple pathways in STAD, such as those related to the extracellular matrix, extracellular structure organization, and extracellular matrix organization. The differentially expressed genes were related to immune infiltration via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways. The western blotting and RT-qPCR results suggested that COL3A1 was overexpressed in STAD tissues compared with normal tissues.Conclusion: COL3A1, ADAMTS12, BGN, FNDC1, AEBP1 and HTRA3 could play important roles in the tumorigenesis and progression of STAD via various pathways, including those involving the extracellular matrix, extracellular structure organization, and extracellular matrix organization. COL3A1, ADAMTS12, BGN, FNDC1, AEBP1, and HTRA3 act as oncogenes in most cancers and may be biomarkers. Additionally, the identification of COL3A1 as a candidate biomarker provides a direction for further research on the role of tumor immunity in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Construction of Prognostic Prediction Model for Stomach Adenocarcinoma Based on the TCGA Database.

Gu¹,

Chen²,

Wang³

2020

Preprint

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“…Our recent study demonstrated that the expression of miR-196b is up-regulated NSCLC, and is negatively regulated by RNA binding protein QKI-5, a tumor suppressor in NSCLC. miR-196b promotes NSCLC progression and metastasis by targeting the tumor suppressors, TSPAN12, GATA6, and FAS (Liang et al, 2020 ) (Huang et al, 2020 ). However, Tellez et al reported that miR-196b-5p was epigenetically silenced in the premalignant stage of lung cancer, suggesting that tumor-suppressive functions of miR-196b in NSCLC (Tellez et al, 2016 ).…”

Section: Tumor Suppressor and Oncogenic Mirnas In Nsclcmentioning

confidence: 99%

Frontiers of MicroRNA Signature in Non-small Cell Lung Cancer

Zhu

Kudo

Huang

et al. 2021

Front. Cell Dev. Biol.

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Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer cases. Recent advancements in diagnostic tools, surgical treatments, chemotherapies, and molecular targeted therapies that improved the therapeutic efficacy in NSCLC. However, the 5-years relative survival rate of NSCLC is only about 20% due to the inadequate screening methods and late onset of clinical symptoms. Dysregulation of microRNAs (miRNAs) was frequently observed in NSCLC and closely associated with NSCLC development, progression, and metastasis through regulating their target genes. In this review, we provide an updated overview of aberrant miRNA signature in NSCLC, and discuss the possibility of miRNAs becoming a diagnostic and therapeutic tool. We also discuss the possible causes of dysregulated miRNAs in NSCLC.

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“…miR-20a inhibits the expression of Fas in osteosarcoma cells, thereby facilitating the survival of tumor cells and enhancing their metastatic capacity [ 33 ]. Besides, miR-146a and miR-196b inhibit Fas expression, and ectopic expression of miR-196b causes rapid leukemia [ 34 , 35 ]. In addition, the expression of miR-196b-5p has been shown to possess a significant negative correlation with the expression of Fas in non-small cell lung cancer (NSCLC) [ 35 ].…”

Section: The Role Of Micrornas In Apoptotic Pathwaysmentioning

confidence: 99%

“…Besides, miR-146a and miR-196b inhibit Fas expression, and ectopic expression of miR-196b causes rapid leukemia [ 34 , 35 ]. In addition, the expression of miR-196b-5p has been shown to possess a significant negative correlation with the expression of Fas in non-small cell lung cancer (NSCLC) [ 35 ]. miR-25, which has been observed to directly target DR4 and protect against TRAIL-mediated apoptosis, is upregulated in intrahepatic bile duct cancer [ 36 ].…”

Section: The Role Of Micrornas In Apoptotic Pathwaysmentioning

confidence: 99%

The role of microRNAs in cell death pathways

Jang

Lee

2021

Yeungnam Univ J Med

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MicroRNAs (miRNAs) are a class of noncoding RNAs that negatively regulate target messenger RNAs. In multicellular eukaryotes, numerous miRNAs perform basic cellular functions, including cell proliferation, differentiation, and death. Abnormal expression of miRNAs weakens or modifies various apoptosis pathways, leading to the development of human cancer. Cell death occurs in an active manner that maintains tissue homeostasis and eliminates potentially harmful cells through regulated cell death processes, including apoptosis, autophagic cell death, and necroptosis. In this review, we discuss the involvement of miRNAs in regulating cell death pathways in cancers and the potential therapeutic functions of miRNAs in cancer treatment.

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miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling

Cited by 28 publications

References 44 publications

Construction of Prognostic Prediction Model for Stomach Adenocarcinoma Based on the TCGA Database.

Construction of Prognostic Prediction Model for Stomach Adenocarcinoma Based on the TCGA Database.

Frontiers of MicroRNA Signature in Non-small Cell Lung Cancer

The role of microRNAs in cell death pathways

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