Upregulation of long non‑coding RNA CCAT2 indicates a poor prognosis and promotes proliferation and metastasis in intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (IHCC) is an aggressive cancer with a poor survival rate and is the second most common type of primary cancer of the hepatobiliary system. At present, the molecular mechanisms of IHCC initiation and progression remain unclear. Recent evidence has indicated that long non‑coding RNAs (lncRNAs) serve a crucial role in cancer development; however, the functional role of lncRNAs in IHCC has not been investigated in detail. In the present study, a marked overexpression of lncRNA colon cancer‑associated transcript 2 (CCAT2) was observed in IHCC cell lines and clinical specimens. Statistical analysis of IHCC clinicopathological characteristics and CCAT2 expression data revealed that high CCAT2 expression levels correlated with microvascular invasion, differentiation grade, tumor (T), lymph node (N), metastasis (M) and overall TNM stages of IHCC (P<0.05). Kaplan‑Meier analysis demonstrated that CCAT2 upregulation was associated with poor overall survival and progression‑free survival in IHCC. Furthermore, high CCAT2 expression was identified as an independent risk factor of IHCC poor prognosis in both univariate and multivariate Cox regression analyses. The role of CCAT2 in promoting IHCC cell proliferation, motility and invasion was further confirmed with in vitro assays. Therefore, CCAT2 may promote IHCC progression and metastasis, and may be a promising prognostic biomarker and therapeutic target in IHCC.

Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma

“…CRNDE, UCA1, TUG1) was reported to correlate with clinical progression (e.g. tumor grade, lymph node metastasis, TNM stage) and was identified as risk factors for an unfavorable overall survival (OS) in iCCA 16,18,[20][21][22][23] .…”

Functions and roles of long noncoding RNA in cholangiocarcinoma

“…Further experiments showed that silencing CCAT2 caused cancer suppressive effects through inhibiting cellular proliferation, migration and invasion, accelerating cellular apoptosis, and reversing EMT process Xu, Y. et al, 2018aXu, Y. et al, , 2018b. In addition, enhanced CCAT2 expression was also associated with microvascular invasion, high differentiation grade, and advanced TNM stage confirmed by Bai's research team (Bai et al, 2018). According to these findings, CCAT2 plays a crucial role in CCA progression and shows advantageous characteristics to be an indicator for early diagnosis and prognosis evaluation.…”

<p>lncRNAs as potential molecular biomarkers in the clinicopathology and prognosis of cholangiocarcinoma: a systematic review and meta-analysis</p>

“…Only four studies found that lncRNAs were significantly associated with histological grade of CCA, while 13 studies claimed that lncRNAs were significantly correlated with tumor grade of CCA. Interestingly, Table 1 shows that AFAP1-AS1 and CCAT2 expressions were significantly related to vascular invasion 11,28. Additionally, ten studies demonstrated that lncRNAs were significantly associated with lymph node metastasis, while three studies reported that lncRNAs were significantly correlated with distant metastasis.…”