LOC101929709 promotes gastric cancer progression by aiding LIN28B to stabilize c-MYC mRNA

Background: LIN28B plays a critical role in the Warburg effect. However, its underlying mechanism remains elusive. Recently, it has been reported that LIN28B could collaborate with IGF2BP3, which can bind to m6A-modified c-Myc transcripts. Therefore, this study investigated if LIN28B recognises methylated c-Myc mRNA to promote the Warburg effect in gastric Cancer.

Methods: Effects of LIN28B on gastric Cancer were confirmed in vitro and in vivo. On the basis of bioinformatics analysis, the association between LIN28B and c-Myc mRNA was shown using RNA immunoprecipitation (RIP) and luciferase reporter assays. The role of m6A was identified by RNA pull-down assays. We further performed RIP-seq to search for long non-coding RNAs (lncRNAs) participating in the LIN28B binding process. Chromatin immunoprecipitation was used to show the impact of c-Myc on transcription of LIN28B and lncRNAs.

Results: LIN28B was identified to stabilize c-Myc mRNA by recognizing m6A. Furthermore, the interaction between c-Myc mRNA and LIN28B is speculated to be supported by LOC101929709, which binds to both LIN28B and IGF2BP3. Functional experiments revealed that LOC101929709 promotes the proliferation, migration and glycolysis of gastric Cancer. Mechanistically, LOC101929709 enriched in the cytoplasm helps LIN28B stabilize c-Myc mRNA. Moreover, c-Myc promoted the transcription of both LOC101929709 and LIN28B. Additionally, LOC101929709 also activated the PI3K/Akt pathway.

Conclusions: The c-Myc/LOC101929709/LIN28B axis promotes aerobic glycolysis and tumour progression. Thus, LOC101929709 can be a novel potential target for gastric Cancer treatment.

Gastric cancer; LIN28B; LOC101929709; The Warburg effect; c-MYC.