Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial-to-mesenchymal transition in lung adenocarcinoma.

The long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) has been identified as an oncogene in multiple types of human malignancy, and the aberrant expression of CCAT1 has been associated with the tumorigenesis and progression of cancer. However, the underlying mechanism of how CCAT1 affects malignant behaviors in lung adenocarcinoma cells remains unknown. In the current study, the expression of CCAT1 was identified to be increased in lung adenocarcinoma tissues (n=96) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and its expression level was associated with epidermal growth factor receptor (EGFR) expression (P=0.011), lymphatic metastasis (P=0.003) and tumor node metastasis (TNM) stage (P=0.003). In vitro, by using Transwell assays, the overexpression of CCAT1 was demonstrated to promote the migration and invasion of H358 lung adenocarcinoma cells; while downregulation of CCAT1 expression inhibited H1650 cell migration and invasion. Furthermore, western blot analysis indicated that aberrant CCAT1 expression may induce epithelial-to-mesenchymal transition (EMT) by regulating the expression levels of EMT markers (E-cadherin, N-cadherin and vimentin). In conclusion, these results indicate that CCAT1 is able to promote the metastasis of lung adenocarcinoma cells by inducing EMT.

[1]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[2]  Xu Zhou,et al.  Aberrant Expression of CCAT 1 Regulated by c-Myc Predicts the Prognosis of Hepatocellular Carcinoma , 2015 .

[3]  Wenxing Zhao,et al.  Long non-coding RNA CARLo-5 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients , 2017, Clinical and Experimental Medicine.

[4]  Yan Zhang,et al.  Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative modulation of miRNA-218-5p , 2015, Cell Death and Disease.

[5]  Xuefei Shi,et al.  The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma , 2015, Oncotarget.

[6]  C. Croce,et al.  Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5 , 2014, Proceedings of the National Academy of Sciences.

[7]  Alexander Stojadinovic,et al.  Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence , 2013, BMC Cancer.

[8]  Long-Bang Chen,et al.  Long noncoding RNA CCAT1 acts as an oncogene and promotes chemoresistance in docetaxel-resistant lung adenocarcinoma cells , 2016, Oncotarget.

[9]  Bing Li,et al.  LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p. , 2016, Cancer letters.

[10]  Jun Lu,et al.  Aberrant Expression of CCAT1 Regulated by c-Myc Predicts the Prognosis of Hepatocellular Carcinoma. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[11]  R. Rosell,et al.  Lung cancer: Maintenance therapy and precision medicine in NSCLC , 2013, Nature Reviews Clinical Oncology.

[12]  Lei Chen,et al.  Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer , 2014, Journal of Neuro-Oncology.

[13]  E. Giovannetti,et al.  Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. , 2014, Cancer treatment reviews.

[14]  Junhui Ge,et al.  Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus , 2014, Cell Research.

[15]  J. Beermann,et al.  Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. , 2016, Physiological reviews.

[16]  L. Tang,et al.  Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer , 2014, Tumor Biology.

[17]  Feng Yang,et al.  Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma , 2013, Journal of Cancer Research and Clinical Oncology.

[18]  Ming Sun,et al.  Long Noncoding RNA ANRIL Promotes Non–Small Cell Lung Cancer Cell Proliferation and Inhibits Apoptosis by Silencing KLF2 and P21 Expression , 2014, Molecular Cancer Therapeutics.

[19]  R. Craven,et al.  Pathways driving the endocytosis of mutant and wild-type EGFR in cancer , 2014, Oncoscience.

[20]  Xian-jun Feng,et al.  Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. , 2014, International journal of clinical and experimental pathology.

[21]  S. Digumarthy,et al.  Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors , 2011, Science Translational Medicine.

[22]  A. Whetton,et al.  The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. , 2014, Cancer treatment reviews.

[23]  Gongchao Wang,et al.  The long noncoding RNA LINC01207 promotes proliferation of lung adenocarcinoma. , 2015, American journal of cancer research.

[24]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.