scholarly journals Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET

2019 ◽  
Vol 216 (6) ◽  
pp. 1377-1395 ◽  
Author(s):  
Yanhan Jia ◽  
Joaquim Si-Long Vong ◽  
Alina Asafova ◽  
Boyan K. Garvalov ◽  
Luca Caputo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Nuclear Structure ◽  
Epithelial Mesenchymal Transition ◽  
Lung Tumor ◽  
Cancer Diagnostics ◽  
Tumor Formation ◽  
Lung Epithelial Cells ◽  
Mesenchymal Transition ◽  
Lamin B1

Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial–mesenchymal transition, cell migration, tumor growth, and metastasis. Mechanistically, we show that lamin B1 recruits the polycomb repressive complex 2 (PRC2) to alter the H3K27me3 landscape and repress genes involved in cell migration and signaling. In particular, epigenetic derepression of the RET proto-oncogene by loss of PRC2 recruitment, and activation of the RET/p38 signaling axis, play a crucial role in mediating the malignant phenotype upon lamin B1 disruption. Importantly, loss of a single lamin B1 allele induced spontaneous lung tumor formation and RET activation. Thus, lamin B1 acts as a tumor suppressor in lung cancer, linking aberrant nuclear structure and epigenetic patterning with malignancy.

scholarly journals FERMT3 mediates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoshan Su ◽  
Junjie Chen ◽  
Xiaoping Lin ◽  
Xiaoyang Chen ◽  
Zhixing Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Migration ◽  
Cigarette Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Control Group ◽  
Data Set ◽  
Mesenchymal Transition

Abstract Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial–mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated. Methods The present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT. Results Based on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling. Conclusions In summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial–mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

scholarly journals lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

2018 ◽  
Vol 48 (5) ◽  
pp. 1928-1941 ◽  
Author(s):  
Chuan He ◽  
Zhigang Liu ◽  
Li Jin ◽  
Fang Zhang ◽  
Xinhao Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

scholarly journals STYK1/NOK Promotes Metastasis and Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer by Suppressing FoxO1 Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanyang Lai ◽  
Fang Lin ◽  
Xuejiao Wang ◽  
Jiao Zhang ◽  
Jinghua Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

AimsSerine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects.MethodsSerine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT in vitro and in vivo. In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC.ResultsSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT.ConclusionSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.

scholarly journals Blockage of TGF-α Induced by Spherical Silica Nanoparticles Inhibits Epithelial-Mesenchymal Transition and Proliferation of Human Lung Epithelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
YiXun Li ◽  
Huan Li ◽  
Yong Duan ◽  
XueMei Cai ◽  
DingYun You ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Cells ◽  
Lung Adenocarcinoma ◽  
Silica Nanoparticles ◽  
Bituminous Coal ◽  
Mononuclear Cells ◽  
Epithelial Mesenchymal Transition ◽  
Lung Epithelial Cells ◽  
Mesenchymal Transition ◽  
Spherical Silica

Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were cocultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, and 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.

scholarly journals LncRNA SRA mediates cell migration, invasion, and progression of ovarian cancer via NOTCH signaling and epithelial-mesenchymal transition

2021 ◽  
Author(s):  
Lee Kyung Kim ◽  
Sun-Ae Park ◽  
Yoolhee Yang ◽  
Young Tae Kim ◽  
Tae-Hwe Heo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Gynecological Cancer ◽  
Notch Pathway ◽  
Tumor Formation ◽  
High Expression ◽  
Free Survival ◽  
Mesenchymal Transition

Long non-coding RNA (lncRNA) is a newly identified regulator of tumor formation and tumor progression. The function and expression of lncRNAs remain to be fully elucidated, but recent studies have begun to address their importance in human health and disease. The lncRNA, SRA, known as Steroid receptor activator, acts as an important modulator of gynecological cancer, and its expression may affect biological functions including proliferation, apoptosis, steroid formation and muscle developments. However, it is still not well known whether SRA is involved in the regulation of ovarian cancer. This study investigated the molecular function and association between SRA expression and clinicopathological factors. In ovarian cancer cell lines, SRA knockdown and overexpression regulated cell migration, proliferation, and invasion. Both in vivo and in vitro experiments using knockdown and overexpression showed that SRA potently regulated epithelial-mesenchymal transition and NOTCH pathway components. Further, clinical data confirmed that SRA was a significant predictor of overall survival and progression-free survival and patients with ovarian cancer exhibiting high expression of SRA exhibited higher recurrence rates than patients with low SRA expression. In conclusion, this study indicates that SRA has clinical significance as its expression can predict the prognosis of ovarian cancer patients. High expression of the lncRNA SRA is strongly correlated with recurrence-free survival of ovarian cancer patients.

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