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

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Xiangjie Huang ◽  
Sisi Xiao ◽  
Xinping Zhu ◽  
Yun Yu ◽  
Meng Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Nsclc Tissue ◽  
Cancer Cell Growth ◽  
Tissue Samples ◽  
Stat3 Signaling ◽  
Transcription 3

Abstract Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with the miR-196b-5p expression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.

scholarly journals USP46 inhibits cell proliferation in lung cancer through PHLPP1/AKT pathway

2020 ◽  
Author(s):  
Wei Wang ◽  
Meng Chen ◽  
Hailing Xu ◽  
Dongqing Lv ◽  
Suna Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Akt Pathway ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Knock Down

Abstract Background: USP46 has been shown to function as tumor suppressor in colon cancer and renal cell carcinoma. However, its specific role in other cancers remains unknown. This study was aimed to investigate the role of USP46 in lung cancer tumorigenesis, and to identify the underlying mechanism. Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western Blotting (WB) were used to measure the expression levels of USP46 and PHLPP1 in lung cancer tissue and adjacent normal tissue from lung cancer patients. The functional role of USP46 in regulating proliferation in lung cancer cells were examined by cell proliferation assay, radiation assay, genetic overexpression and knock down and chemical inhibition of relevant genes. The underlying mechanisms were investigated in multiple lung cancer cell line models by co-immunoprecipitation and ubiquitination assays. Results: This study identified strong downregulation of USP46 and PHLPP1 expression in lung cancer tissues relative to normal adjacent tissues. USP46 was further shown to inhibit lung cancer cell proliferation under normal growth conditions and during radiation induced DNA damage by antagonizing the ubiquitination of PHLPP1 resulting in the inhibition of AKT signaling. The effect of USP46 knock down on lung cancer cell proliferation was significantly reversed by exposure to radiation and AKT inhibition. Conclusions: USP46 is down-regulated in lung cancer, and it suppresses proliferation of lung cancer cells by inhibiting PHLPP1/AKT pathway. AKT inhibition slows proliferation of USP46 down-regulated lung cancer cells exposed to radiation suggesting a potential therapeutic avenue for USP46 down-regulated lung cancer through a combination of radiation and AKT inhibitor treatment.

scholarly journals KRT6A Promotes Lung Cancer Cell Growth and Invasion Through MYC-Regulated Pentose Phosphate Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Di Che ◽  
Mingshuo Wang ◽  
Juan Sun ◽  
Bo Li ◽  
Tao Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pentose Phosphate Pathway ◽  
Mammalian Cells ◽  
Pentose Phosphate ◽  
Nsclc Tissue ◽  
Cancer Cell Growth ◽  
Tissue Samples ◽  
Patient Prognosis

Keratin 6A (KRT6A) belongs to the keratin protein family which is a critical component of cytoskeleton in mammalian cells. Although KRT6A upregulation in non-small cell lung cancer (NSCLC) has been reported, the regulatory mechanism and functional role of KRT6A in NSCLC development have been less well investigated. In this study, KRT6A was confirmed to be highly expressed in NSCLC tissue samples, and its high expression correlated with poor patient prognosis. Furthermore, overexpression of KRT6A promotes NSCLC cell proliferation and invasion. Mechanistically, KRT6A overexpression is sufficient to upregulate glucose-6-phosphate dehydrogenase (G6PD) levels and increase the pentose phosphate pathway flux, an essential metabolic pathway to support cancer cell growth and invasion. In addition, we discovered that lysine-specific demethylase 1A (LSD1) functions upstream to promote KRT6A gene expression. We also found that the MYC family members c-MYC/MYCN are involved in KRT6A-induced G6PD upregulation. Therefore, this study reveals an underappreciated mechanism that KRT6A acts downstream of LSD1 and functions as a pivotal driver for NSCLC progression by upregulating G6PD through the MYC signaling pathway. Together, KRT6A and LSD1 may serve as potential prognostic indictors and therapeutic targets for NSCLC.

scholarly journals Dasatinib Inhibits Lung Cancer Cell Growth and Patient Derived Tumor Growth in Mice by Targeting LIMK1

2020 ◽  
Vol 8 ◽  
Author(s):  
Man Zhang ◽  
Jie Tian ◽  
Rui Wang ◽  
Mengqiu Song ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth

Lung cancer is a leading cause cancer-related death with diversity. A promising approach to meet the need for improved cancer treatment is drug repurposing. Dasatinib, a second generation of tyrosine kinase inhibitors (TKIs), is a potent treatment agent for chronic myeloid leukemia (CML) approved by FDA, however, its off-targets and the underlying mechanisms in lung cancer have not been elucidated yet. LIM kinase 1 (LIMK1) is a serine/threonine kinase, which is highly upregulated in human cancers. Herein, we demonstrated that dasatinib dose-dependently blocked lung cancer cell proliferation and repressed LIMK1 activities by directly targeting LIMK1. It was confirmed that knockdown of LIMK1 expression suppressed lung cancer cell proliferation. From the in silico screening results, dasatinib may target to LIMK1. Indeed, dasatinib significantly inhibited the LIMK1 activity as evidenced by kinase and binding assay, and computational docking model analysis. Dasatinib inhibited lung cancer cell growth, while induced cell apoptosis as well as cell cycle arrest at the G1 phase. Meanwhile, dasatinib also suppressed the expression of markers relating cell cycle, cyclin D1, D3, and CDK2, and increased the levels of markers involved in cell apoptosis, cleaved caspase-3 and caspase-7 by downregulating phosphorylated LIMK1 (p-LIMK1) and cofilin (p-cofilin). Furthermore, in patient-derived xenografts (PDXs), dasatinib (30 mg/kg) significantly inhibited the growth of tumors in SCID mice which highly expressed LIMK1 without changing the bodyweight. In summary, our results indicate that dasatinib acts as a novel LIMK1 inhibitor to suppress the lung cancer cell proliferation in vitro and tumor growth in vivo, which suggests evidence for the application of dasatinib in lung cancer therapy.

scholarly journals HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation

2021 ◽  
Vol 22 (11) ◽  
pp. 5506
Author(s):  
Hye Guk Ryu ◽  
Youngseob Jung ◽  
Namgyu Lee ◽  
Ji-Young Seo ◽  
Sung Wook Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Camp Response Element Binding ◽  
Cancer Cell Proliferation ◽  
Hnrnp A1 ◽  
Lung Carcinogenesis ◽  
Lung Cancer Cell ◽  
Cis Acting

Heterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3′ untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element–binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3′UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.

USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN

2017 ◽  
Vol 441 (1-2) ◽  
pp. 1-7 ◽  
Author(s):  
Jia Sun ◽  
Tianxiang Li ◽  
Yinying Zhao ◽  
Lirong Huang ◽  
Hua Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Lung Cancer Cell ◽  
Cancer Cell Growth
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