Abstract
Long non-coding RNAs (LncRNAs) are a group of RNAs that are more than 200 nt in length but cannot encode proteins. Accumulating evidences showed that abnormal LncRNA expressions are highly involved in many kinds of tumor. By using gene trap methods which could knockdown gene expression to find important genes, we found one LncRNA which called intergenic non-protein coding RNA 52 (LINC00052) has the ability to inhibit invasion and migration of hepatocarcinoma cells. We found that invasion, migration and proliferation abilities in SMMC7721 cell were inhibited after up-expressing LINC00052. We identified that NTRK3 was the target gene of LINC00052. Down-expression of NTRK3 could increase SMMC7721 cell invasion, migration and proliferation. Meanwhile, we discovered that LINC00052 could regulate NTRK3 expression by forming complementary base pairing with miR-128 and miR-485-3p to reduce the luciferase activity of NTRK3 3′UTR. These results reveal a new mechanism for understanding hepatocarcinoma cells invasion and migration.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor and the third leading cause of cancerrelated deaths worldwide [1]
For finding new gene which has a function in HCC cells invasion and migration, gene trapping vector PU21 were transfected into SMMC77221 hepatoma cells and selected by G418
Studies have shown that Long non-coding RNAs (LncRNAs) participate in a wide variety of molecular genetics and cellular processes, including chromosomal dosage compensation, control of imprinting, chromatin modification, chromatin structure, transcription, splicing, Figure 5: LINC00052 modulated NTRK3 expression by interacting with miR-128 and miR-485-3p. (A) Expressions of microRNAs which involved in regulating MTRK3 were checked in low LINC00052 expression (A554 cells) and high LINC00052 expression cells. (B) miR-128 and miR-485-3p could form complementary bases with LINC00052 and NTRK3 3′UTR. (C), (D) Over expression miR-128 and miR-485-3p were constructed and verified by real-time PCR. (E) Luciferase activity of NTRK3 3′UTR were detected after cotransfected with pTarget-miR-128, pTarget miR-485-3p and pcDNA3.1-LINC00052. pTarget, pcDNA3.1 and pGL3-control were used as controls
Summary
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor and the third leading cause of cancerrelated deaths worldwide [1]. At least three categories of metastasis genes have been proposed to facilitate the multistep metastatic cascade: (1) “initiation” genes that facilitate detachment (e.g., CDH2 (encodes N-Cadherin) and TWIST), extracellular matrix degradation (e.g., MMPs) or angiogenesis (e.g., VEGF); (2) “progression” genes (e.g., PTGS2 (encodes COX-2) and MMP-1) that regulate extravasation of circulating tumor cells and are involved in metastatic colonisation; (3) “virulence” genes (e.g., IL6 and TNFα), which promote survival in circulation, and/or provide a proliferative advantage in the distant microenvironment. We found LINC00052 through gene trapping technique and found its ability to regulate invasion and migration in HCC cells. We reported that LINC00052 could inhibit HCC cells invasion and migration through complementing with miR128 and miR-485-3p, both of them can regulate NTRK3 [10](neurotrophic tyrosine kinase receptor, type 3) gene expression. Our results elucidated that LINC00052 might have a tumor suppressor function in HCC and could be a novel potential target for therapy of HCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: 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.
