Abstract
Though the long noncoding RNA colon cancer associated transcript-1 (CCAT-1) has been shown to be involved in tumors of other tissues, its involvement in cervical cancer is still unknown. Therefore, the aim of this study was to investigate the molecular mechanism of CCAT-1 in cervical cancer. We quantified the expression of CCAT-1 long noncoding RNA in samples of cervical cancer tissue by real-time PCR. Effects of CCAT-1 expression on the proliferation and apoptosis of HeLa and CaSki cells were assessed by cell-count, colony-formation, and flow cytometry assays. Binding of the c-Myc protein to the CCAT-1 promoter was confirmed by chromatin immunoprecipitation. Finally, TOP-Flash and western blotting were used to examine the regulation of the Wnt/β-catenin pathway by CCAT-1. The results showed that compared with adjacent normal tissue, the expression of CCAT-1 in cervical cancer tissue was significantly upregulated. CCAT-1 expression was related to the stage and size of the tumor and recurrence prognosis. Then, we showed through functional assays that CCAT-1 could promote proliferation and inhibit apoptosis of cervical cancer cells. Furthermore, chromatin immunoprecipitation showed that c-Myc protein could promote CCAT-1 expression by binding to its promoter. Finally, fluorescent-reporter assays and western blotting showed that CCAT-1 could activate the Wnt/β-catenin pathway. In conclusion, we showed that CCAT-1 can be activated by the c-Myc protein and it can promote proliferation and inhibit apoptosis in cervical cancer cells by regulating the Wnt/β-catenin pathway. CCAT-1 might serve as a good prognostic indicator and target for treatment of cervical cancer.
Highlights
Cervical cancer is the fourth most common malignancy in women worldwide
Expression levels of cancer associated transcript-1 (CCAT-1) in cervical cancer tissues (n=94) and matched, adjacent, normal tissues were detected by quantitative real-time PCR
No significant relationship was observed between CCAT-1 levels and other parameters such as age and menopausal status of the patients, histological organization of the tissue, degree of differentiation, depth of invasion, lymphatic vascular space invasion (LVSI), and lymph node metastasis of the tumor (Table 1)
Summary
Cervical cancer is the fourth most common malignancy in women worldwide. There are approximately 500,000 new cases of cervical cancer and 233,000 deaths caused by it per year [1]. Cervical cancer is a major health problem worldwide. A deeper understanding of the genetic mechanisms that control the progression of the disease is imperative for enabling early clinical diagnosis and effective treatment of cervical cancer patients. LncRNAs are RNA molecules that are longer than 200 nucleotides in length and contain no proteincoding capacity [2]. Increasing evidence suggests that lncRNAs are involved in tumorigenic processes such as cell proliferation, apoptosis, differentiation, and invasion in [3, 4] in cervical cancer [5, 6], retinoblastoma [7], and oral squamous cell carcinoma [8]
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