Coexpression of UCA1 and ITGA2in pancreatic cancer cells target the expression of miR‐107 through focal adhesion pathway

Abstract

Objectives Abnormal expressions of microRNAs (miRNAs) are demonstrated in pancreatic cancer (PaC), but a major part of the mechanism remains elusive. This study mainly aimed to structure a coexpressed network of long noncoding RNA (lncRNA) and messenger RNA (mRNA) in PaC, as well as to explore their direct targets. Methods LncRNA and mRNA microarrays were used to determine the expression profiles in PaC cells. Analysis of Kyoto Encyclopedia of Genes and Genomes pathway was performed to identify pathways associated with differentially expressed mRNAs. Coexpression profiles were identified by constructing differentially expressed lncRNA‐mRNA regulatory network and further validated by quantitative real‐time polymerase chain reaction assay and western blot assay. The bioinformatics computational method was applied to predict the biological target of lncRNA and mRNA, which was identified by luciferase reporter assay. Migration/invasion ability and apoptosis rate of cells were assessed by transwell assay and flow cytometry assay. Results It was identified that the level of urothelial cancer associated 1 (UCA1) was increased in PaC cells, and the inhibition of UCA1 suppressed migration and invasion ability of the cancer cells. The luciferase reporter assay recognized that miR‐107 was targeted by UCA1, and integrin subunit α 2 (ITGA2) was further targeted by miR‐107. This confirmed the prediction of lncRNA‐miRNA‐mRNA regulation mechanism. In the regulatory pathways, UCA1 and ITGA2 promoted PaC progression via focal adhesion pathway related proteins such as ITGA3, SRC protooncogene/nonreceptor tyrosine kinase, protein tyrosine kinase 2, and AKT serine/threonine kinase 1. Conclusion The study revealed a regulatory network of UCA1‐miR‐107‐ITGA2 and validated UCA1 and ITGA2 as potential prognostic factors for PaC.

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.…”

Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

“…29,30 The expression of lncRNA UCA1 has been reported to be upregulated in many cancers, including breast cancer, 21,22 colorectal cancer, 31 hepatocellular carcinoma 32 and GC. 33,34 Interestingly, lncRNA UCA1 was found to be participating in cell cycle by targeting mRNA CCNE1 and CDK1 through miR-107 as well. Although this pathway has not been elucidated until now, the inhibition of UCA1 suppressed migration and invasion ability of the cancer cells through a regulatory network of UCA1-miR-107-ITGA2 in pancreatic cancer has been confirmed.…”

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

“…Pancreatic cancer is a highly aggressive malignant tumor with the characteristic of hepatic metastasis [73]. UCA1 promoted migration of pancreatic cancer by sponging miR-107 targeting integrin subunit a 2 (ITGA2) [74]. Moreover, UCA1 could promote pancreatic cancer cell multiplication and metastatic ability by down-regulating miR-96 and up-regulating forkhead box O3 (FOXO3).…”