Overexpression of long non‑coding RNA CRNDE facilitates epithelial‑mesenchymal transition and correlates with poor prognosis in intrahepatic cholangiocarcinoma

Abstract

The clinical significance and essential role of long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) have been well illuminated in various cancers. However, the function of CRNDE in intrahepatic cholangiocarcinoma (IHCC) has not been reported at present. The aim of the present study was to investigate the role of CRNDE in IHCC. Firstly, the relative expression of CRNDE was observed to be upregulated in IHCC cell lines and tissues. And high CRNDE expression was statistically associated with IHCC differentiation grade, lymph node metastasis, tumor-nodes-metastasis (TNM) stage and size. Survival analysis identified that high CRNDE expression is a predictor of worse overall survival (OS) and progression-free survival (PFS) in patients with IHCC. Moreover, high CRNDE expression was identified as an independent risk factor of IHCC poor OS and PFS. Further studies of in vitro assays suggested that CRNDE silencing could suppress the proliferation of HuCCT1 cells following CCK-8 and colony formation assays, while CRNDE ectopic expression in HCCC9810 cells promoted proliferation. Moreover, the migration and invasion of HuCCT1 cells were greatly repressed with CRNDE deficiency following Transwell and Matrigel assays. Accordingly, the motility of HCCC9810 cells was notably accelerated with CRNDE overexpression. Mechanistically, CRNDE was revealed to facilitate the epithelial-mesenchymal transition (EMT) of IHCC cells. In conclusion, these observations indicated that CRNDE could promote the clinical progression and metastasis of IHCC by facilitating EMT. CRNDE may be a novel prognostic marker and therapeutic target in IHCC.

LncRNA CRNDE is a biomarker for clinical progression and poor prognosis in clear cell renal cell carcinoma

“…40 Wang et al suggested that CRNDE overexpression was related with shorter overall survival in pancreatic cancer cases. 33 In addition, patients with colorectal cancer with high CRNDE level has a lower overall survival rates than patients with low CRNDE level, and high-expression CRNDE was an independent prognostic indicator for colorectal cancer cases. 33 In addition, patients with colorectal cancer with high CRNDE level has a lower overall survival rates than patients with low CRNDE level, and high-expression CRNDE was an independent prognostic indicator for colorectal cancer cases.…”

“…Moreover, high level of CRNDE expression served as a predictor of worse overall survival and progression free survival in patients with intrahepatic cholangiocarcinoma. 33 In addition, patients with colorectal cancer with high CRNDE level has a lower overall survival rates than patients with low CRNDE level, and high-expression CRNDE was an independent prognostic indicator for colorectal cancer cases. 36,37 In glioma, high-expression of CRNDE was also found to be associated with poor prognosis, and as an independent prognostic factor for overall survival.…”

“…Besides, we further investigate the clinical value of CRNDE in patients with ccRCC through estimating the relationship between CRNDE expression and clinicopathological characteristics. 33 Moreover, Wang et al revealed that CRNDE expression appeared to have positive correlation with tumor differentiation, tumor size, TNM stage, and lymph nodal metastasis in patients with pancreatic cancer. Similarly, Han et al reported that high levels of CRNDE expression were associated with large tumor size, lymph node metastasis, and poor pathological grade in patients with colorectal cancer.…”

“…7 In renal cell carcinoma, Shao et al performed loss-of-function and gain-of-function assays and found that CRNDE enhanced the cell proliferation and growth both in vitro and in vivo through regulating Wnt/β-catenin signaling. 26,33 To investigate the molecular mechanism of CRNDE in regulating ccRCC cell motility, we found that CRNDE positively regulated the protein expression of Vimentin, ZEB1 and ZEB2, and negatively modulated E-cadherin protein expression. In our study, loss-offunction and gain-of-function approaches were performed to estimate the effect of CRNDE on ccRCC cell migration and invasion.…”

Functions and roles of long noncoding RNA in cholangiocarcinoma

“…| 17119 differentially expressed (CRNDE; Xia et al, 2018), cancer susceptibility candidate 15 (CASC15; Merdrignac et al, 2018), and highly upregulated in liver cancer (HULC; Wang et al, 2016) are overexpressed in CCA and contribute to malignant phenotypes of CCA cells. These results illustrate that they perform regulatory roles in the pathological process and molecular mechanism of CCA.…”