Long non‑coding RNA CCAT2 promotes prostate cancer cell proliferation and invasion by regulating the Wnt/β‑catenin signaling pathway

Abstract

Long non-coding RNA colon cancer associated transcript 2 (CCAT2) is dysregulated in a number of different types of human cancer, and affects cancer progression via the Wnt/β-catenin signaling pathway. However, the roles of CCAT2 and the Wnt/β-catenin signaling pathway in prostate cancer (PCa) are not completely understood. The present study aimed to investigate the potential mechanism of CCAT2 in PCa. In the present study, the reverse transcription-quantitative PCR (RT-qPCR) results indicated that CCAT2 expression was significantly upregulated in PCa tissues, and DU145 and PC3 cell lines compared with normal prostate tissues and the epithelial RWPE-1 cell line, respectively. Functional assays indicated that CCAT2 downregulation inhibited DU145 and PC3 cell proliferation, cell cycle, migration and invasion. In addition, the luciferase reporter assay, RT-qPCR and western blotting results indicated that CCAT2 regulated transcription factor 7 like 2 (TCF7L2) expression by binding to microRNA-217. Further western blotting and TOPFlash assays indicated that CCAT2-knockdown inhibited the Wnt/β-catenin signaling pathway in DU145 and PC3 cell lines by inhibiting the expression of TCF7L2. However, CCAT2-knockdown-mediated effects were reversed by the Wnt/β-catenin signaling pathway activator lithium chloride (LiCl). Further cell experiments suggested that LiCl treatment reversed CCAT2-knockdown-mediated inhibition of PCa cell proliferation, cell cycle, epithelial-mesenchymal transition, migration and invasion. Overall, the results indicated that CCAT2 regulated PCa via the Wnt/β-catenin signaling pathway; therefore, CCAT2 may exhibit key role during the progression of PCa and may serve as a therapeutic target for the disease.

The Roles of the Colon Cancer Associated Transcript 2 (CCAT2) Long Non-Coding RNA in Cancer: A Comprehensive Characterization of the Tumorigenic and Molecular Functions

“…This interplay between CCAT2, MYC, and WNT molecules has been explored and confirmed in multiple cancers in recent years and is responsible for the main pro-tumorigenic roles of CCAT2. Similar studies confirmed the presence of the mechanism in the case of thyroid [27], ovarian [28], clear cell renal cell carcinoma [29], and breast cancers [30].…”

LncRNA ELFN1-AS1 Promotes Retinoblastoma Growth and Invasion via Regulating miR-4270/SBK1 Axis

“… 9 LncRNA CCAT2 initiates prostate cancer proliferation and metastasis through activation of Wnt signaling. 10 LncRNA LINC00491 promotes lung cancer proliferation, migration and invasion by sponging miR-324 to facilitate SP1 expression. 11 Thus, it is important to determine the correlation between lncRNA and RB progression.…”

Knockdown of long non-coding RNA CCAT2 suppresses growth and metastasis of esophageal squamous cell carcinoma by inhibiting the β-catenin/WISP1 signaling pathway

“… 11 In prostate cancer, knockdown of CCAT2 reduced Wnt/β-catenin signaling by inhibiting the expression of TCF7L2. 29 Cai et al. reported that suppressing the expression of CCAT2 in breast cancer cells decreased the translational levels of β-catenin both in the cytoplasm and nucleus.…”

“…11 In prostate cancer, knockdown of CCAT2 reduced Wnt/b-catenin signaling by inhibiting the expression of TCF7L2. 29 Cai et al reported that suppressing the expression of CCAT2 in breast cancer cells decreased the translational levels of b-catenin both in the cytoplasm and nucleus. 13 Guo et al reported that knockdown of CCAT2 in glioma cells suppressed b-catenin translocation from the cytoplasm to the nucleus, while there was little effect on the total cellular b-catenin levels.…”