ABSTRACT
BACKGROUND: Recently, more and more evidence indicated that the long non-coding RNA was strictly related to the occurrence and progression of human cancers, including esophageal cancer (EC). We observed that LINC00667 was increased in EC, but the function of LINC00667 was unclear. Therefore, the function and potential molecular mechanism of LINC00667 in the progression of EC need to be further studied. METHODS: Quantitative real-time PCR was used to investigate the levels of LINC00667, miR-200b-3p, and SLC2A3. The levels of protein involved in cell cycle, cell apoptosis, epithelial-mesenchymal transition, as well as SLC2A3 were quantitatived by western blot. The role of LINC00667 in the proliferative, migratory and invasive capabilities of EC cells were measured by cell counting kit-8 assay, EdU assay, flow cytometry assay, wound healing assay and transwell assay, respectively. Interaction between LINC00667 and miR-200b-3p or miR-200b-3p and SLC2A3 were confirmed using a luciferase reporter assay. RESULTS: In this work, we found that LINC00667 expression was up-regulated in EC cell lines, and LINC00667 knockdown inhibited cell proliferation, migration, and invasion in EC cells. In addition, it showed that LINC00667 functioned as competitive endogenous RNA for miR-200b-3p by the DIANA-LncBase database. Moreover, we used targetscan online software to predict SLC2A3 as a target gene of miR-200b-3p. Subsequently, rescue experiments confirmed that knocking out SLC2A3 could reverse the inhibitory effect of miR-200b-3p on EC cells transfected with sh-LINC00667. CONCLUSION: Herein, we revealed the novel mechanism of LINC00667 on regulating metastasis-related gene by sponge regulatory axis during EC metastasis. Our results demonstrated that LINC00667 plays a critical role in metastatic EC by mediating sponge regulatory axis miR-200b-3p/SLC2A3. To explore function of LINC00667/miR-200b-3p/SLC2A3 axis may provide an informative biomarker of malignancy and a highly selective anti-EC therapeutic target.
Subject(s)
Esophageal Neoplasms , MicroRNAs , RNA, Long Noncoding , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition/genetics , Esophageal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Glucose Transporter Type 3/genetics , Glucose Transporter Type 3/metabolism , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
PURPOSE: To uncover the role of LINC01980 in aggravating the progression of hepatocellular carcinoma (HCC) via targeting caspase 9. METHODS: The expression levels of LINC01980 and caspase 9 in HCC tissues and paracancer tissues were determined by qRT-PCR. The prognostic potentials of LINC01980 and caspase 9 in HCC were assessed by Kaplan-Meier method. The regulatory effects of LINC01980 and caspase 9 on the viability, clonality and apoptosis of Huh7 and Hep3B cells were examined. Finally, the interaction between LINC01980 and caspase 9 was evaluated by performing dual-luciferase reporter gene assay and rescue experiments. RESULTS: LINC01980 was upregulated in HCC tissues and cells. High level of LINC01980 indicated worse prognosis in HCC patients. Knockdown of LINC01980 could attenuate viability and clonality, but induced apoptosis in Huh7 and Hep3B cells. Caspase 9 was downregulated in HCC, and its high level predicted a better prognosis in HCC patients. Overexpression of caspase 9 achieved the same regulatory effects as LINC01980 knockdown on HCC cells. Caspase 9 was the downstream target for LINC01980, and its level was negatively regulated by LINC01980. In HCC, LINC01980 regulated HCC cell behaviors by downregulating caspase 9. CONCLUSIONS: Upregulation of LINC01980 in HCC predicts a poor prognosis. LINC01980 aggravates the progression of HCC via downregulating caspase 9.
