Dataset Information

Speckle-type POZ protein functions as a tumor suppressor in non-small cell lung cancer due to DNA methylation.

ABSTRACT:

Background

Tumor suppressor epigenetic silencing plays an important role in non-small cell lung cancer (NSCLC) development and progression. Previously, the expression of speckle-type POZ protein (SPOP) has been found to be significantly inhibited in NSCLC. Our research aimed to investigate the molecular mechanisms, clinical significance and epigenetic alteration of SPOP in NSCLC.

Materials and methods

Bisulfite sequencing PCR and methylation-specific PCR were performed to test gene methylation. Chromatin immunoprecipitation (ChIP) was performed to detect transcription factor C/EBP? combinations and the promoter of the SPOP gene. Furthermore, we evaluated the effects of C/EBP? siRNA on SPOP expression, tumor cell migration and proliferation via MTT and Transwell assays in vitro and tumor growth in vivo. The relationship between the methylation status of the SPOP gene and clinicopathologic characteristics was investigated.

Results

Hypermethylation was found in the CpG island of the SPOP gene promoter in NSCLC tissues, and this methylation was found to be correlated with SPOP expression. SPOP promoter methylation was associated with the pathology grade. The transcriptional activities were significantly inhibited by the hypermethylation of specific CpG sites within the SPOP gene promoter, while 5-aza-2'-deoxycytidine significantly increased SPOP gene expression. C/EBP? also played a key role in SPOP regulation. Five C/EBP? binding sites in the CpG island of the SPOP gene promoter were identified by ChIP. Inhibition of C/EBP? significantly reduced SPOP expression. SPOP mediated the C/EBP?-regulated suppression of invasion, migration and proliferation in vitro and tumor growth in vivo.

Conclusions

SPOP function and expression in NSCLS were regulated by DNA methylation and C/EBP? transcriptional regulation combination effects, indicating that the SPOP promoter methylation status could be utilized as an epigenetic biomarker and that the C/EBP?-SPOP signaling pathway could be a potential therapeutic target in NSCLC.

SUBMITTER: Yao S

PROVIDER: S-EPMC6304003 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Speckle-type POZ protein functions as a tumor suppressor in non-small cell lung cancer due to DNA methylation.

Yao Sumei S Chen Xinming X Chen Jinliang J Guan Yangbo Y Liu Yifei Y Chen Jianrong J Lv Xuedong X

Cancer cell international 20181222

<h4>Background</h4>Tumor suppressor epigenetic silencing plays an important role in non-small cell lung cancer (NSCLC) development and progression. Previously, the expression of speckle-type POZ protein (SPOP) has been found to be significantly inhibited in NSCLC. Our research aimed to investigate the molecular mechanisms, clinical significance and epigenetic alteration of SPOP in NSCLC.<h4>Materials and methods</h4>Bisulfite sequencing PCR and methylation-specific PCR were performed to test gen ...[more]

PMID: 30607139

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Project description:Background aimsGastric cancer is the most frequent gastrointestinal tumor in adults and is the most lethal form of human cancer. Despite of the improvements in treatments, the underlying mechanism of gastric carcinogenesis is not well known. To define novel modulators that regulate susceptibility to tumorgenesis, we focused on miR-219-2-3p.MethodsQuantitative RT-PCR was employed to investigate the level of miR-219-2-3p in gastric cancer (GC) tissues (n = 113) and their matched adjacent normal tissues (n = 113). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate biological effects of miR-219-2-3p. Since silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorgenesis, GC cells were treated with 5-aza-2'-deoxycytidine and trichostatin A, and expression changes of miR-219-2-3p were subsequently examined by quantitative RT-PCR. Finally, the methylation status of CpG island upstream of miR-219-2-3p was analyzed by methylation-specific PCR in GC tissues (n = 22).ResultsmiR-219-2-3p was down-regulated in GC and cell lines. In addition, the experiments documented the lower expression of miR-219-2-3p in GC specimens with higher grade and later stage tumors. Meanwhile, miR-219-2-3p exerted antiproliferative, proapoptotic, and antimetastatic roles and reduced levels of p-ERK1/2 in GC cells. Furthermore, 5-aza-2'-deoxycytidine and trichostatin A increased the expression (~2 fold) of miR-219-2-3p in GC cells. By methylation-specific PCR, DNA methylation in the upstream region of miR-219-2-3p was detected in both adjacent normal tissues and cancer tissues. As expected, the methylation level was considerably higher in the miR-219-2-3p down-regulated group than up-regulated group.ConclusionsmiR-219-2-3p is potentially involved in gastric cancer progression and metastasis by regulating ERK1/2-related signal pathways, which may provide a novel therapeutic strategy for treatment of gastric cancer. Methylation mechanism may be involved in modulating the expression level of miR-219-2-3p in gastric cancer.

Dataset Information

Speckle-type POZ protein functions as a tumor suppressor in non-small cell lung cancer due to DNA methylation.

Background

Materials and methods

Results

Conclusions

Publications

Speckle-type POZ protein functions as a tumor suppressor in non-small cell lung cancer due to DNA methylation.

Similar Datasets

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