Long non-coding RNA CCAT2 functions as an oncogene in hepatocellular carcinoma, regulating cellular proliferation, migration and apoptosis

Zhou, Ning; Si, Zhongzhou; Li, Ting; Chen, Guangshun; Zhang, Zhongqiang; Qi, Haiyun

doi:10.3892/ol.2016.4580

Cited by 54 publications

(41 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several lncRNAs, including LINC00152, GHET1, HULC, HOTAIR, GACAT3, MALAT2 and H19, have been demonstrated to serve as oncogenes, whereas other lncRNAs, including LEIGC, GAS5 and FER1L4, have been considered to be tumor suppressors (10). Emerging evidence indicated that CCAT2 functions as a cancer-promoting molecule in several types of solid cancer, such as in non-small cell lung cancer (11), oral squamous cell carcinoma (12), ovarian cancer (13), and hepatocellular carcinoma (14). The present study investigated the effects of the lncRNA CCAT2 on the biological behavior of BGC-823 cells, and revealed that knockdown of CCAT2 expression effectively inhibited the proliferation, as well as induced the apoptosis and autophagy of GC cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells

Lee

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

The role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of tumors has been receiving increasing attention. Colon cancer-associated transcript 2 (CCAT2), a type of oncogenic lncRNA, is regarded as a novel biomarker of poor prognosis and metastasis in various types of cancer. However, the molecular contributions of CCAT2 to gastric cancer (GC) progression remain largely unclear. The aim of the present study was to demonstrate the effect of silencing CCAT2 on the biological behavior of GC BGC-823 cells and illustrate the potential underlying molecular mechanisms. A short hairpin RNA interference plasmid pRNAT-U6.1-CCAT2 targeting CCAT2 was successfully constructed. At 48 h after transfection with the interference plasmid, the survival rate of BGC-823 cells was significantly decreased, as determined by the MTT assay. In addition, RT-qPCR results revealed that CCAT2 gene expression was effectively suppressed by the transfection, while POU domain class 5 transcription factor 1B (POU5F1B) gene expression was significantly decreased. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay further revealed that the apoptotic index was significantly higher in the interference group. Western blot analysis also demonstrated that the expression of beclin-1 protein was significantly increased, whereas the expression levels of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) proteins were downregulated in the interference group. In conclusion, CCAT2 was able to positively regulate the expression of POU5F1B gene. Furthermore, silencing of CCAT2 gene inhibited the proliferation of BGC-823 cells, as well as induced apoptosis and autophagy in BGC-823 cells, by suppression of the PI3K/mTOR signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells

Lee

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…Recently, studies have indicated that dysregulation of lncRNA involved in the biologic processes of tumor [ 21 ]. In HCC, Long non-coding RNA CCAT2 functions as an oncogene in hepatocellular carcinoma, regulating cellular proliferation, migration and apoptosis [ 22 ]. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA CARLo-5 promotes tumor progression in hepatocellular carcinoma via suppressing miR-200b expression

et al. 2017

View full text Add to dashboard Cite

Long non-coding RNAs (lncRNAs) play key roles in cancer initiation and progression. The aim was to investigate the biological functions and clinical significance of long non-coding RNA CARLo-5 in hepatocellular carcinoma (HCC). QRT-PCR was performed to investigate CARLo-5 expression in HCC tissues and cells. Kaplan-Meier curve and multivariate analysis validated the association between CARLo-5 expression and overall survival (OS) in HCC patients. Cell proliferation and invasion was performed by CCK8 cell proliferation, cell colony formation and transwell invasion assays. Western-blot assay was performed to evaluate the protein expression of Twist1, ZEB1, E-cadherin and Vimentin. Tumor xenografts were performed to evaluate the effect of CARLo-5 on tumor growth in vivo. RNA Immunoprecipitation (RIP) and Chromatin Immunoprecipitation (ChIP) were also performed. Our results showed that CARLo-5 expression was significantly higher in HCC tissues and upregulated CARLo-5 expression was closely correlated with tumor size and advanced tumor stage. Kaplan-Meier curve and multivariate analysis validated that higher CARLo-5 expression predicted a poor prognosis for HCC patients and was an independent risk factor for OS in HCC patients. In vitro, knockdown of CARLo-5 inhibited cell proliferation, colony formation, cell invasion and inhibited the cell epithelial-mesenchymal transition (EMT) by up-regulating the E-cadherin expression and down-regulating Twist1, ZEB1 and vimentin expression in HCC cells. Furthermore, we demonstrated that CARLo-5 inhibited the miR-200b expression via EZH2. In vivo, knockdown of CARLo-5 significantly inhibited the tumor growth. Thus, our results indicated that CARLo-5 represented a novel tumor biomarker and therapeutic target for HCC.

show abstract

“…These studies suggest that CCAT2 gene may act as a novel oncogene in these tumors,regulating celluar growth,migration and apoptosis. Moreover, abnormal expression of CCAT2 was suggested to be associated with lymph node metastasis,distant metastasis and overall survival [ 17 ] . Therefore, we performed this meta-analysis to investigate the lymph node metastasis, distant metastasis and clinical prognostic role of overexpression CCAT2 in human cancers.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA CCAT2 as a novel biomaker of metastasis and prognosis in human cancer: a meta-analysis

Wang

Chen

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Colon cancer-associated transcript2 (CCAT2), a long noncoding RNA (LncRNA), has been found to function as an oncogene in various cancers. However, the clinical value of CCAT2 in cancers remains unclear. Therefore, we performed this meta-analysis to investigate the association between CCAT2 level and metastasis & prognosis in malignant tumors. The meta analysis was performed by using a systematic search in PubMed, Web of Science, and Cochrane Library from inception to NOV 17, 2016. According to the inclusion and exclusion criteria,9 studies with 1084 patients were included in the meta-analysis.The result showed that overexpression of CCAT2 is positively correlated with lymph node metastasis (Odds ratio,OR=3.57, 95 % confidence interval(CI): 1.79-7.13, p<0.001) in a random-effects model (I2=71%, p=0.008) and distant metastasis(OR=7.68, 95 % CI: 3. 29-17.96, p<0.001) in a random-effects model (I2=41.9%, p=0.16).Likewise,we also found that high CCAT2 expression could predict unfavourable overall survival with pooled hazard ratio (HR) of 2.23 (95 % CI 1.68-2.96, p<0.00001) by a random-effects model (I2=37.5%, p=0.143) and poor metastasis-free survival in cancer patients (HR= 2.08, 95%CI:1.37-3.18 p=0.001) by a fixed-effects model (I2=0.0%, p=0.807). In conclusion,CCAT2 might be served as a novel molecular marker for predicting metastasis and prognosis in various human-cancers.

show abstract

Long non-coding RNA CCAT2 functions as an oncogene in hepatocellular carcinoma, regulating cellular proliferation, migration and apoptosis

Cited by 54 publications

References 36 publications

Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells

Effect of silencing colon cancer-associated transcript 2 on the proliferation, apoptosis and autophagy of gastric cancer BGC-823 cells

Long non-coding RNA CARLo-5 promotes tumor progression in hepatocellular carcinoma via suppressing miR-200b expression

Long noncoding RNA CCAT2 as a novel biomaker of metastasis and prognosis in human cancer: a meta-analysis

Contact Info

Product

Resources

About