Upregulation of CCAT2 promotes cell proliferation by repressing the P15 in breast cancer.

Long non-coding RNAs (lncRNAs) are demonstrated to function as modulators of both transcriptional and post-transcriptional regulation in various types of tumors progression. The objective of the study is to investigate the clinical significance and underlying mechanism of Colon cancer associated transcript 2 (CCAT2) involved in breast cancer. QT-PCR was performed to examine the relative expression levels of CCAT2 in breast cancer tissues and adjacent normal tissues. Kaplan-Meier survival curves and log rank test were applied to assess the correlation between CCAT2 expression and the overall survival (OS) time in patients. MTT cell proliferation assay, transwell invasion assay and cell cycle analysis were conducted to detect the cell proliferation and invasion. Western blot analysis, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays were performed to detect the association between CCAT2 and P15. The tumor xenograft in nude mice was performed to evaluate the effect of CCAT2 expression on tumor growth in vivo. Our results confirmed that CCAT2 expression levels in tumor tissues were markedly increased than that in adjacent normal tissues. Higher CCAT2 expression was found to show a significantly correlation with advanced TNM stage and lymph node metastasis in patients. Kaplan-Meier survival curves and log-rank test showed that higher CCAT2 expression was closely correlated with shorter over survival (OS) time in patients. In vitro, knockdown of CCAT2 showed that cell proliferation and invasion capabilities were suppressed and increased G0-G1 phase cell proportion but reduced S phase cell proportion in MCF-7 and MDA-MB-231 cells. Moreover, when CCAT2 silencing, the cell cycle relative protein CyclinD1, CyclinE1 and CDK4 expression were downregulated, but p15 was up-regulated in MCF-7 and MDA-MB-231 cells. Besides, we confirmed that CCAT2 suppressed the p15 expression level via interacting with EZH2 in breast cancer cells. In vivo, the tumor growth was inhibited after knockdown of CCAT2. Our results indicated that CCAT2 may be a potential prognostic marker and therapeutic target for breast cancer.

Deng X ，Zhao Y ，Wu X ，Song G ... -  《-》

The long non-coding RNA CCAT2 is up-regulated in ovarian cancer and associated with poor prognosis.

Huang S ，Qing C ，Huang Z ，Zhu Y ... -  《Diagnostic Pathology》

Long non-coding RNA CCAT2 promotes cell proliferation and invasion through regulating Wnt/β-catenin signaling pathway in clear cell renal cell carcinoma.

Huang JL ，Liao Y ，Qiu MX ，Li J ，An Y ... -  《-》

Long non-coding RNA GHET1 promotes human breast cancer cell proliferation, invasion and migration via affecting epithelial mesenchymal transition.

Song R ，Zhang J ，Huang J ，Hai T ... -  《-》

LncRNA CCAT2 enhances cell proliferation via GSK3β/β-catenin signaling pathway in human osteosarcoma.

Ruan R ，Zhao XL 《-》