Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

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miR-103 Functions as a Tumor Suppressor by Directly Targeting Programmed Cell Death 10 in NSCLC

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15000757094686 ◽

2018 ◽

Vol 26 (4) ◽

pp. 519-528 ◽

Cited By ~ 10

Author(s):

Dong Yang ◽

Jian-Jun Wang ◽

Jin-Song Li ◽

Qian-Yu Xu

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Death ◽

Programmed Cell Death ◽

Tumor Size ◽

Apoptotic Cell ◽

A549 Cells ◽

Invasion And Migration ◽

Metastatic Capacity ◽

And Migration

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Absence of miR-103 has recently been identified to be associated with metastatic capacity of primary lung tumors. However, the exact role of miR-103 in NSCLC and the molecular mechanism are unclear. In the present study, we showed that miR-103 expression was reduced in NSCLC tissues and cells. miR-103 expression was negatively correlated with tumor size and stage. The overall survival was longer in patients with higher miR-103 level than in those with lower miR-103 expression. miR-103 inhibited cell proliferation in A549 cells, decreased tumor weight and volume, and prolonged survival of tumor-implanted nude mice. miR-103 increased apoptotic cell death in A549 cells. Furthermore, miR-103 decreased the invasion and migration abilities in A549 cells, as evidenced by Transwell and wound healing results. Downregulation of miR-103 significantly reduced the level of programmed cell death 10 (PDCD10). We found a significant decrease in the relative luciferase activity of the reporter gene in A549 cells cotransfected with the miR-103 mimic and pGL3-PDCD10 WT 3′-UTR, but not pGL3-PDCD10 mut 3′-UTR. We showed that overexpression of PDCD10 significantly inhibited miR-103-induced inhibition of cell proliferation, increased apoptosis, and decreased invasion and migration in A549 cells. Moreover, we found that PDCD10 expression was increased in NSCLC tissues and cells. PDCD10 expression was positively correlated with tumor size and stage. Overexpression of PDCD10 increased cell proliferation and inhibited apoptosis in A549 cells. The data demonstrated that dysregulation of the miR-103/PDCD10 signal may be a novel therapeutic target for the treatment of NSCLC.

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Targeting ZEB2 By microRNA-129 In Non-Small Cell Lung Cancer Suppresses Cell Proliferation, Invasion And Migration Via Regulating Wnt/β-Catenin Signaling Pathway And Epithelial–Mesenchymal Transition

OncoTargets and Therapy ◽

10.2147/ott.s217536 ◽

2019 ◽

Vol Volume 12 ◽

pp. 9165-9175 ◽

Cited By ~ 5

Author(s):

Xingtao Li ◽

Chunhong Li ◽

Hongmei Bi ◽

Shufang Bai ◽

Lin Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration

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Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-205778 ◽

2019 ◽

Vol 73 (3) ◽

pp. 139-146

Author(s):

Hao-Ran Li ◽

Bai-Quan Qiu ◽

Jian Gao ◽

Chun Jin ◽

Jia-Hao Jiang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Western Blot ◽

Blot Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Invasion And Migration ◽

And Migration ◽

The Relationship

AimsTo unveil the role of EI2BL in non-small cell lung cancer (NSCLC) and the relationship between expression of EI2BL and the prognosis of patients with NSCLC.MethodsImmunohistochemistry (IHC), western blot analysis, immunofluorescence and real-time quantitative PCR (RT-qPCR) were used to evaluate EI2BL protein and mRNA levels in NSCLC and corresponding peritumour tissues. Cell Counting Kit-8, transwell assay and wound healing assay were used to analyse the abilities of cell proliferation, invasion and migration. In addition, the analysis of epithelial-mesenchymal transition (EMT) markers was also assessed by western blot analysis, RT-qPCR and immunofluorescence. Tissue micro-array analysis of 200 NSCLC cases was used to assess the relationship between EI2BL expression and clinicopathological characteristics. Moreover, the prognostic role of EI2BL in 200 patients with NSCLC was evaluated by Cox regression models and Kaplan-Meier methods.ResultsElevated EI2BL expression was more common in NSCLC tissues than paired peritumour tissues in both mRNA and protein level. EI2BL promoted the proliferation, invasion and migration of NSCLC cells. In addition, aberrant EI2BL expression might modulate the expression of key molecules of EMT by ERK1/2 signal pathway. The expression of EI2BL was significantly associated with tumour stage, lymph node metastasis and tumour size. Moreover, higher expression of EI2BL in patients with NSCLC had a poor overall survival rate.ConclusionsOur study illustrated that elevated expression of EI2BL promoted NSCLC cell proliferation, migration and invasion and EI2BL overexpression may be a reliable biomarker of poor prognosis.

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