The up-regulation of long non-coding RNA CCAT2 indicates a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition

JinFeng, Zheng; Zhao, Shaoxiong; He, Xijing; Zheng, Zhili; Bai, Weibin; Duan, Youlin; Cheng, Shanlin; Wang, Juncai; Liu, Xucheng; Zhang, Gang

doi:10.1016/j.bbrc.2016.08.120

Cited by 71 publications

(66 citation statements)

References 27 publications

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“…Unigene56159 can act as a competing endogenous RNA to decrease the expression of Slug by interacting with miR-140-5p [31]. In addition, upregulation of colon cancer-associated transcript 2 predicts poor prognosis in patients with prostate cancer and promotes metastasis by regulating the EMT [32]. In this study, we found that LncDQ promoted cell proliferation and motility via the EMT pathway, indicating that LncDQ acts as an oncogene in HCC.…”

Section: Discussionmentioning

confidence: 68%

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Zeng

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are key regulators of cancer initiation and progression. In this study, we investigated the clinical value and functional role of LncRNA DQ786243 (LncDQ) in the pathogenesis of hepatocellular carcinoma (HCC). Methods: To investigate the expression level of LncDQ in HCC, we performed quantitative real-time PCR using total RNA extracted from HCC tumor tissues and their matched non-neoplastic counterparts, as well as from the serum of HCC patients and healthy volunteers. The correlation of LncDQ expression with clinicopathologic features and prognosis was analyzed. The functional role of LncDQ in cell proliferation, migration, and invasion were evaluated by MTT cell viability, wound healing, and transwell assays in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays were performed to analyze the potential mechanism of LncDQ in HCC cells. Results: LncDQ was upregulated in both HCC tissue samples and serum and was correlated with low survival rate and adverse clinical pathological characteristics. Multivariate analysis demonstrated that LncDQ expression was an independent prognostic factor for HCC. The area under the receiver operating characteristic curve was 0.804 with a sensitivity of 0.72 and a specificity of 0.8. Knockdown of LncDQ induced inhibition of cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, LncDQ regulated the epithelial–mesenchymal transition pathway by interacting with EZH2, to epigenetically repress the expression of E-cadherin in HCC cells. Conclusions: Taken together, the results of our study indicate that LncDQ plays a critical role in HCC progression, and may serve as a potential diagnostic and prognostic biomarker for HCC.

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Section: Discussionmentioning

confidence: 68%

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Zeng

Lin

et al. 2018

Cell Physiol Biochem

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“…Remarkably, other studies also demonstrated that CCAT1 or CCAT2 knockdown through siRNAs inhibit cell growth, migration, and invasion in PC-3 and DU145 cells [21,43], indicating that CCAT1/2 silencing mimics VIRMA knockdown in metastatic androgen-independent PCa cells.…”

Section: Discussionmentioning

confidence: 85%

VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer

Barros‐Silva

Lobo

Guimarães‐Teixeira

et al. 2020

Cancers

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RNA methylation at position N6 in adenosine (m6A) and its associated methyltransferase complex (MTC) are involved in tumorigenesis. We aimed to explore m6A biological function for long non-coding RNAs (lncRNAs) in prostate cancer (PCa) and its clinical significance. m6A and MTC levels in PCa cells were characterized by ELISA and western blot. Putative m6A-regulated lncRNAs were identified and validated by lncRNA profiler qPCR array and bioinformatics analysis, followed by m6A/RNA co-immunoprecipitation. Impact of m6A depletion on RNA stability was assessed by Actinomycin D assay. The association of m6A-levels with PCa prognosis was examined in clinical samples. Higher m6A-levels and VIRMA overexpression were detected in metastatic castration-resistant PCa (mCRPC) cells (p < 0.05). VIRMA knockdown in PC-3 cells significantly decreased m6A-levels (p = 0.0317), attenuated malignant phenotype and suppressed the expression of oncogenic lncRNAs CCAT1 and CCAT2 (p < 0.00001). VIRMA depletion and m6A reduction decreased the stability and abundance of CCAT1/2 transcripts. Higher expression of VIRMA, CCAT1, and CCAT2 as a group variable was an independent predictor of poor prognosis (HR = 9.083, CI95% 1.911–43.183, p = 0.006). VIRMA is a critical factor sustaining m6A-levels in PCa cells. VIRMA downregulation attenuates the aggressive phenotype of PCa by overall reduction of m6A-levels decreasing stability and abundance of oncogenic lncRNAs.

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“…Only two studies reported no association between increased CCAT2 expression and LNM in prostate cancer and bladder cancer, respectively, which might be caused by the small size or the tumor type 17, 23. The mechanism on regulatory activity of CCAT2 in cancer invasion and metastasis has been explored in several cancer types.…”

Section: Discussionmentioning

confidence: 99%

“…High expression of CCAT2 has been reported associated with metastasis and prognosis in different types of cancer, which indicated the diagnostic or prognostic value of CCAT2 for cancer 13-16, 20, 22, 23. However, the results from each study were insufficient and not completely consistent in the correlation between CCAT2 and the clinical metastatic factors (as lymph node metastasis (LNM) and distance metastasis (DM)) or prognostic factors (like OS and progression free survival (PFS)).…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA CCAT2 as a Potential Novel Biomarker to Predict the Clinical Outcome of Cancer Patients: A Meta-Analysis

Tan¹,

Hou²,

Fu³

et al. 2017

J. Cancer

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Background: Colon Cancer-Associated Transcript 2 (CCAT2) has been demonstrated associated with clinical outcomes in various tumors. However, the results from each study were unfortunately insufficient and not completely consistent. Therefore, we conduct a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis.Methods: A meta-analysis was performed using data obtained through a systematic search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang database and VIP database. The pooled odds ratio (OR) and hazard ratio (HR) with 95% Confidence interval (CI ) using random-effect were used to identify the relationship of CCAT2 with clinical outcome of cancer patients. Subgroup analysis and sensitivity analysis were performed.Results: A total of 867 patients from eight studies were finally included. Patients with high CCAT2 expression underwent an increased risk of lymph node metastasis (LNM) (OR=3.09, 95% CI: 1.53-6.26) and distant metastasis (DM) (OR=7.70, 95% CI: 3.26-18.17). CCAT2 was also significantly correlated with overall survival (OS) (HR=2.19, 95%CI: 1.70-2.82) and progression-free survival (PFS) (HR=2.59, 95% CI: 1.78-3.76). Moderate heterogeneity was observed in meta-analysis for LNM. However, the results remained robust in multiple sensitivity analyses.Conclusions: High expression of CCAT2 was linked with poor clinical outcome. CCAT2 can serve as a potential molecular marker for prognosis in different types of cancers.

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The up-regulation of long non-coding RNA CCAT2 indicates a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition

Cited by 71 publications

References 27 publications

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer

Long Noncoding RNA CCAT2 as a Potential Novel Biomarker to Predict the Clinical Outcome of Cancer Patients: A Meta-Analysis

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