Upregulated long non-coding RNA BC032469 enhances carcinogenesis and metastasis of esophageal squamous cell carcinoma through regulating hTERT expression
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Currently, long non-coding RNAs (lncRNAs) have been shown to have critical regulatory roles in various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Here, we focused on lncRNA BC032469, one of the lncRNAs involved in the development of ESCC. The levels of a specific differentially expressed lncRNA (termed lncRNA-BC032469) were measured in 45 paired esophageal squamous cell carcinoma tissue samples by quantitative real-time RT-PCR and then subjected to correlation analysis with clinical parameters and prognosis. The functions of lncRNA-BC032469 were evaluated by silencing and overexpressing the lncRNA in vitro and in vivo. The expression level of BC032469 in esophageal squamous cell carcinoma tissues was higher than that in the corresponding non-cancerous tissues. High BC032469 levels were correlated with lymph node metastasis, TNM stage, and tumor size and lower overall survival. Knockdown of BC032469 in TE13 and Eca109 cells inhibited cell proliferation, migration, and invasion; induced cell cycle arrest in the G0/G1 phase; and promoted apoptosis. Western blot analysis revealed that BC032469 regulated the expression of human telomerase reverse transcriptase (hTERT), which is important for cell proliferation and metastasis. Moreover, the restored expression of hTERT protein in BC032469-knockdown cells attenuated the suppressive effects of BC032469 on ESCC cells. Collectively, these results indicated that lncRNA-BC032469 is an oncogenic lncRNA that promotes tumor progression and leads us to propose that lncRNAs may serve as key regulatory hubs in ESCC development.
KeywordsEsophageal squamous cell carcinoma LncRNAs lncRNA-BC032469 hTERT Proliferation Invasion Prognosis
Compliance with ethical standards
This study was approved by the Ethics Committee of Changhai Hospital, Second Military Medical University, and written informed consent was obtained from each patient. All animal research protocols were approved by the Animal Care and Use Ethics Committee of Second Military Medical University.
Conflicts of interest
- 3.Pennathur A, Farkas A, Krasinskas AM, Ferson PF, Gooding WE, Gibson MK, et al. Esophagectomy for T1 esophageal cancer: outcomes in 100 patients and implications for endoscopic therapy. Ann Thorac Surg. 2009;87(4):1048–54 discussion 54-5. doi: 10.1016/j.athoracsur.2008.12.060.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Cui F, Wu D, He X, Wang W, Xi J, Wang M. Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016. doi: 10.1007/s13277-016-4962-9.Google Scholar
- 30.Yang G, Rosen DG, Mercado-Uribe I, Colacino JA, Mills GB, Bast Jr RC, et al. Knockdown of p53 combined with expression of the catalytic subunit of telomerase is sufficient to immortalize primary human ovarian surface epithelial cells. Carcinogenesis. 2007;28(1):174–82. doi: 10.1093/carcin/bgl115.CrossRefPubMedGoogle Scholar
- 33.Deblakshmi RK, Deka M, Saikia AK, Sharma BK, Singh N, Das NN, et al. Prognostic relevance of human telomerase reverse transcriptase (hTERT) expression in patients with gall bladder disease and carcinoma. Asian Pacific journal of cancer prevention : APJCP. 2015;16(7):2923–8.CrossRefPubMedGoogle Scholar
- 34.Safont MJ, Gil M, Sirera R, Jantus-Lewintre E, Sanmartin E, Gallach S, et al. The prognostic value of hTERT expression levels in advanced-stage colorectal cancer patients: a comparison between tissue and serum expression. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2011;13(6):396–400. doi: 10.1007/s12094-011-0673-2.CrossRefGoogle Scholar