Abstract
BackgroundLncRNA TUG1 has been reported to be highly expressed in CRC samples and cells and promoted metastasis by affecting EMT, indicating a poor prognosis for colorectal cancer (CRC). In this study, we determined the underlying mechanism for tumor oncogenesis of lncRNA TUG1 in CRC metastasis.MethodsThe expressions of miR-600 and KIAA1199 in 76 CRC patients and CRC cells and CRC metastatic tissues were determined using qRT-PCR. Epithelial-mesenchymal transition (EMT)-related proteins were determined using western blot. CRC cell metastasis was assessed by colony formation, wound healing and transwell assay. Luciferase reporter gene assay was used to confirm miR-600 binding to KIAA1199 3’UTR.ResultsOur data showed that lncRNA TUG1 was upregulated in CRC cells, miR-600 was downregulated in CRC tissues, cell lines and CRC metastatic tissues, and low miR-600 expression predicted a poor clinical prognosis. Overexpression of miR-600 suppressed CRC cell migration/invasion and EMT-related proteins in vitro, inhibited tumor volume and weight, and decreased the number of CRC liver metastasis in vivo. KIAA1199 was upregulated in CRC tissues, and was negatively regulated by miR-600. KIAA1199 overexpression promoted CRC cell migration and invasion, which reversed the inhibition effect of miR-600 mimic on migration and invasion of CRC cells. Moreover, TUG1 negatively regulated miR-600, and inhibition of TUG1 suppressed CRC cell migration and invasion and EMT-related proteins via regulating miR-600.ConclusionOur study proved that TUG1 promoted KIAA1199 expression to accelerate EMT and metastasis of CRC cell through inhibition of miR-600 expression.
Highlights
LncRNA TUG1 has been reported to be highly expressed in CRC samples and cells and promoted metastasis by affecting epithelial-mesenchymal transition (EMT), indicating a poor prognosis for colorectal cancer (CRC)
LncRNA TUG1,miR-600 expressions in CRC and their effect on CRC cells Our previous research found long noncoding RNAs (lncRNAs) TUG1 was upregulated in CRC cell lines and CRC clinical samples, and play a vital role in EMT and migration of CRC [19]
We measured the expression of miR-600 in 76 CRC tissue and adjacent normal tissue, and CRC cell lines (HCT116, SW480, HT29, LOVO, SW620) using qRT-PCR. miR-600 expression was decreased in CRC tissues compared with adjacent normal tissues (Fig. 1a). miR-600 expression was significantly decreased in CRC cell lines than the normal human colon epithelial cell line NCM460, with the lowest miR-600 expression in SW620 cell line and the highest in HCT116 cell line (Fig. 1b)
Summary
LncRNA TUG1 has been reported to be highly expressed in CRC samples and cells and promoted metastasis by affecting EMT, indicating a poor prognosis for colorectal cancer (CRC). We determined the underlying mechanism for tumor oncogenesis of lncRNA TUG1 in CRC metastasis. Colorectal cancer (CRC) is the third most deadly cancer in the United States, which accounts for 8% of all cancer deaths in men and women [1]. Increasing evidences show that epithelial-mesenchymal transition (EMT) plays an important role in the metastasis of CRC. Li et al reported that inhibition of EMT induced the suppression of CRC cell migration and invasion [5]. Vu and Datta reviewed that EMT led to the increase of invasiveness and metastasis in CRC [6]. During EMT, epithelial marker Ecadherin is downregulated, and mesenchymal markers vimentin and N-cadherin are upregulated through regulating different EMT-related signaling pathways [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
