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ABSTRACT
Background: Gastric cancer (GC) is a serious threat for public health worldwide. Long non-coding RNA (lncRNA) linc00152 has been well reported to be an oncogene and a potential biomarker in multiple cancers including GC. However, the molecular mechanisms of linc00152 in GC development need to be further investigated.
Methods: RT-qPCR assay was employed to detect the levels of linc00152, microRNA-193b-3p (miR-193b-3p) and ETS1 mRNA. ETS1 protein level was measured by western blot assay. Cell proliferative, migratory and invasive capacities were assessed by colony formation together with CCK-8 assays, transwell migration and invasion assays, respectively. Bioinformatics analyses and luciferase reporter assay were used to explore whether miR-193b-3p could interact with linc00152 or ETS1 3ʹUTR. The roles and molecular basis of linc00152 silence on the growth of GC xenograft tumors were tested in vivo.
Results: Linc00152 expression was notably upregulated in GC tissues and cells. The proliferative, migratory and invasive abilities of GC cells were weakened by linc00152 depletion, miR-193b-3p overexpression or ETS1 knockdown. Linc00152 upregulation inhibited miR-193b-3p expression by direct interaction and abolished miR-193b-3p-mediated anti-proliferation, anti-migration and anti-invasion effects in GC cells. ETS1 was a target of miR-193b-3p and linc00152 could promote ETS1 expression by downregulating miR-193b-3p. In vivo experiments further validated that linc00152 knockdown inhibited the growth of GC xenograft tumors by upregulating miR-193b-3p and downregulating ETS1.
Conclusion: Knockdown of linc00152 inhibited GC progression by sequestering miR-193b-3p from ETS1 in vitro and in vivo, elucidating a novel molecular mechanism of linc00152 in promoting GC carcinogenesis.
Abbreviations
Gastric cancer (GC); Long non-coding RNA (lncRNA); microRNA; 193b-3p (miR-193b-3p); nucleotides (nt); Small interference RNA (siRNA); Linc00152 overexpression plasmid (pcDNA-linc00152); standard deviations (SD); non-coding RNAs (ncRNAs); miR-193b precursor (pre-miR-193b); head and neck squamous cell carcinomas (HNSCC)
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed
Acknowledgments
Not applicable