| Popis: |
Background: Long noncoding RNA (lncRNA) Can regulates tumor malignant phenotype either as a tumor suppressor or an oncogene. In hepatocellular carcinoma (HCC), the clinical significance and underlying mechanism of LINC00238 function remain undefined. Methods: Down-regulated expression levels of noncoding RNAs were screened from TCGA LIHC dataset through GEPIA software. The expression of RNAs were determined by qRT-PCR. Molecular clone was performed to over-expression and knockdown of LINC00238 expression. The levels of proteins were evaluated via Western blot. The cell viability, clone formation and migration ability were assessed by CCK-8, plate clone formation and Transwell assays. RNA pull down and Luciferase reporter assays were applied to detect the interplays between LINC00992 and miR-3935.Results: LINC00238 was identified as a significant downregulated both in TCGA and in our cohort, and its low expression was significantly correlated with bigger tumor size, early recurrence and poor survival of patients with HCC after surgery. Through the results of gain and loss of function experiments, LINC00238 was confirmed as a tumor suppressor， which could decrease not only cell viability, migration and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down showed that LINC00238 sponged mir-522, and then, released the inhibition effects on two downstream targets, SFRP2 and DKK1.Conclusions: We identified LINC00238 as a tumor suppressor by sponging miR-522 followed by release silencing of downstream targets, suggesting that LINC00238 has a key role in restraining the malignant phenotype of HCC cells and providing a novel perspective on lncRNAs in HCC progression. |
