Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1and activation of the ERK/MAPK signaling pathway

Abstract

In the present study, we aimed to identify specific lncRNAs and miRNAs, as well as mRNAs, involved in bile duct carcinoma (BDC) and to further explore the way in which lncRNA UCA1 regulates cell metastasis ability. Differentially expressed RNAs were screened out from the TCGA database. In in vitro experiments, qRT-PCR was used to measure lncRNA UCA1, miR-122 and CLIC1 expression. We performed a dual luciferase assay to validate the target relationships among UCA1, CLIC1 and miR-122. The cell migration ability was measured by a wound healing assay, and Transwell assays were applied to detect cell invasive ability. Western blot analysis was employed to detect the expression of related proteins in the MAPK signaling pathway. According to the bioinformatics analysis, lncRNA UCA1 and CLIC1 were both significantly upregulated in BDC, while the expression of miR-122 declined compared with the normal group. The target relationship among UCA1, CLIC1 and miR-122 was verified. UCA1 promoted BDC cell migration and invasiveness, while miR-122 inhibited their progression. CLIC1 served as the downstream target gene of miR-122 and had opposite effects. The ERK/MAPK signaling pathway was activated after upregulating UCA1. LncRNA-UCA1 promoted the metastasis of BDC cells by regulating the expression of miR-122 and its downstream gene mRNA CLIC1 and promoted the activation of the ERK/MAPK pathway, which expanded the horizons of targeted therapy of cholangiocarcinoma.

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.…”

“…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.…”

Downregulated lncRNA UCA1 acts as ceRNA to adsorb microRNA-498 to repress proliferation, invasion and epithelial mesenchymal transition of esophageal cancer cells by decreasing ZEB2 expression

“…Jiao et al have found that lncRNA UCA1 is a significant molecular for tumor growth and could be an effective target for EC therapy [9]. Several articles have conveyed that lncRNA UCA1 could perform as a competing endogenous RNA (ceRNA) of some microRNA (miRNAs), such as miR-193a [7] and miR-122 [10]. miRNA-485-5p (miR-485-5p) strained EC tumorigenesis and could provide as a novel candidate for therapeutic applications in EC treatment [11].…”

<p>Down-regulation of lncRNA LINC00152 Suppresses Gastric Cancer Cell Migration and Invasion Through Inhibition of the ERK/MAPK Signaling Pathway</p>

“…16 The relationship between LncRNA and ERK/MAPK signaling pathway has been reported in a variety of cancers, including hepatocellular carcinoma, bile duct carcinoma and lung cancer. [17][18][19] LncRNA PICART1 inhibits cell proliferation by regulating ERK/MAPK signaling pathways in GC. 20 In addition, LncRNA CARLo-5 promotes proliferation and activates the ERK/MAPK pathway in GC.…”