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

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) has been suggested as serving pivotal roles in tumorigenesis. However, the clinical significance and biological role of CCAT2 in ccRCC remains elusive. The purpose of this study is to identify the function of CCAT2 in ccRCC and its possible molecular mechanism. Expression of CCAT2 was analyzed in 61 ccRCC tissues and two ccRCC cell lines (786-O and ACHN) by quantitative reverse transcription polymerase chain reaction. The functional roles of CCAT2 in ccRCC were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, Transwell assay, and flow cytometric analysis. The influence of CCAT2 on tumorigenesis was monitored by in vivo mice xenograft model. The activation of Wnt/β-catenin signaling pathway was evaluated by the TOP/FOP Wnt luciferase reporter assay and western blot assay. CCAT2 expression was markedly higher in ccRCC cell lines and tissues, being positively associated with tumor size and tumor stage in ccRCC patients. Patients with higher CCAT2 expression had a markedly poorer overall survival than did patients with low CCAT2 expression. Knocking down CCAT2 expression led to reduced cell proliferation and increased apoptosis of ccRCC cells in vitro as well as the activation of Wnt/β-catenin signaling pathway, and CCAT2 overexpression remarkably enhanced these oncogenic properties. In vivo mice xenograft model also showed that knocking CCAT2 expression inhibited the growth of ccRCC xenografts. In conclusion, these results indicated that CCAT2 may play a critical role in ccRCC progression and will be further considered as a biomarker for predicting the survival of ccRCC patients and a potential therapeutic target for ccRCC intervention.

Expression signature of six‐snoRNA serves as novel non‐invasive biomarker for diagnosis and prognosis prediction of renal clear cell carcinoma

“…47 In our study, host gene USP34 of SNORA70B was mainly involved in regulating WNT signalling pathway. Moreover, they were involved in renal development and initiation of several renal diseases including kidney malignancy.…”

“…Moreover, they were involved in renal development and initiation of several renal diseases including kidney malignancy. 47 In our study, host gene USP34 of SNORA70B was mainly involved in regulating WNT signalling pathway.…”

RETRACTED ARTICLE: Long non-coding RNA CCAT2 acts as an oncogene in osteosarcoma through regulation of miR-200b/VEGF

“…Recently, large amount of researches have demonstrated that many lncRNAs such as HOTAIR, and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) are highly expressed in colorectal cancer, breast cancer, hepatocellular carcinoma and some other cancer tissues and are closely related to a variety of cancer metastasis, thus can be used as targets for cancer early diagnosis, treatment and prognosis prediction [17,18]. CCAT2, as a novel oncogene, is located in the hotspot of tumour-related rs6983267 SNP, which promotes the occurrence and development of kinds of cancers by affecting Wnt and TGF-b signalling pathways [9,19]. Such as Xie et al reported that CCAT2 was overexpressed in endometrial cancer and knockdown of CCAT2 inhibited endometrial cancer cells growth and metastasis via sponging miR-216b [20].…”

Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status

“…Different long non-coding RNAs (lncRNAs) can also modulate the Wnt pathway at transcriptional to post-translational levels [64]. In a ccRCC cell line, the colon cancer-associated transcript 2 (CCAT2) promoted the ccRCC tumorigenesis [65] whereas LINC01510 negatively governed the canonical pathway and suppressed cell proliferation, invasion, EMT and promoted the apoptosis of ccRCC [66].…”