Long non‑coding RNA UCA1 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells through targeting microRNA‑122

Abstract

Long non-coding RNA urothelial carcinomaassociated 1 (UCA1) has a role in various common types of human malignancy, including cholangiocarcinoma; however, the expression and function of UCA1 in intrahepatic cholangiocarcinoma (ICC) has remained elusive. In the present study, it was observed that UCA1 expression was significantly upregulated in ICC tissues and cell lines compared with that in the adjacent non-tumour tissues and a human intrahepatic biliary epithelial cell line, respectively. The increased expression of UCA1 was significantly associated with lymph node metastasis and clinical T-stage in ICC. Furthermore, the ICC patients with high expression of UCA1 had a shorter survival time when compared with that of patients with low UCA1 expression. Knockdown of UCA1 caused a significant decrease in ICC cell proliferation and invasion, while ectopic overexpression of UCA1 significantly promoted the proliferation and invasion of ICC cells. Furthermore, it was revealed that UCA1 directly binds to microRNA (miR)-122 to negatively regulate its expression in ICC cells. In addition, miR-122 mimics abrogated the promoting effects of UCA1 on ICC cell proliferation and invasion. In addition, an inverse correlation between miR-122 and UCA1 expression in ICC tissues was observed.In conclusion, the present study demonstrates that the lncRNA UCA1 promotes ICC cell proliferation and invasion at least in part by targeting miR-122, suggesting that the UCA1/miR-122 interaction may become a potential therapeutic target for the treatment of ICC.

Long non-coding RNA UCA1 promotes malignant phenotypes of renal cancer cells by modulating the miR-182-5p/DLL4 axis as a ceRNA

“…The Long non-coding RNA UCA1 was located in chromosome 9p13.12, and has been found to be overexpressed in tumor tissues, such as esophageal squamous cell carcinoma,colorectal cancer, ovarian cancer, bile duct carcinoma and melanoma etc. [16][17][18][19][20][21][22][23].UCA1 are participated in the tumorigenesis and progression, functioning as an oncogene [24][25][26][27][28][29][30]. However, the relation between UCA1 and renal cancer is still unknown and mysterious particularly.…”

“…Accumulated evidences indicate the reciprocal inhibition between lncRNAs and miRNAs [16,20,22,24,25,Fig. 9 UCA1 positively regulates DLL4 expression via sponging miR-182-5p.…”

“…Accumulating evidences suggested that long non-coding RNAs (lncRNAs) perform important or vital functions in the malignant tumors [9][10][11][12][13][14][15]. LncRNA urothelial cancer associated 1 (UCA1) is abnormally expressed in esophageal squamous cell carcinoma, colorectal cancer, gastric cancer melanoma cells, pancreatic cancer, thyroid cancer, lung cancer and so on [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. In vitro and in vivo assays were conducted to further explore its underlying roles in tumor progression.…”

Emerging roles of long noncoding RNAs in cholangiocarcinoma: Advances and challenges

“…This mechanism has been confirmed in multiple gastrointestinal cancers but not in cholangiocarcinoma [42]. However, lncRNAs such as PVT1 [43], UCA1 [44], and ANRIL [45], which have been verified to be induced by hypoxia in gastrointestinal cancers [41,42], were also abnormally expressed in CCA, suggesting that further exploration of hypoxia-regulated lncR-NAs in CCA should be carried out.…”

“…On the other hand, the downregulation of several lncRNAs plays the same role in CCA cells including LINC01714 [63], FENDRR [64], MEG3 [65], and MIR22HG [66]. Similarly, in studies of lncRNAs in iCCA, NEF [67], LFAR1 [46], SNHG3 [68], UCA1 [44], CRNDE [69] and CCAT2 [70], and can also facilitate the migration and invasion of iCCA cells (Table 1). invasion, and anti-apoptosis [74] Abbreviations: CCA, cholangiocarcinoma; lncRNA, long noncoding RNA; RUNX1, RUNX family transcription factor 1; EMT, epithelial-to-mesenchymal transition; CDKN1A, cyclin-dependent kinase inhibitor 1A;…”