The SNHG15/miR-451a/Caveolin-1 Axis Promotes Oxaliplatin Resistance in Gastric Cancer Cells by Regulating Fatty Acid β-Oxidation.

Gastric cancer is a common malignant tumor of the digestive tract. Chemotherapy resistance severely limits the therapeutic effect of this disease. The competing endogenous RNA regulatory network is widely involved in the occurrence and development of various cancers and is also closely related to the generation of drug resistance. However, the underlying molecular mechanism remains to be further elucidated. This study investigated the molecular mechanism by which the long noncoding RNA SNHG15/miR-451a/Caveolin-1 (CAV1) axis mediates oxaliplatin resistance in gastric cancer through regulating fatty acid β-oxidation. Through analysis using The Cancer Genome Atlas database and qRT-PCR, it was found that SNHG15 was highly expressed in gastric cancer tissues, whereas miR-451a was lowly expressed. Bioinformatics prediction combined with dual luciferase and RNA immunoprecipitation experiments confirmed that SNHG15 could act as a molecular sponge for miR-451a, and CAV1 was the downstream target gene of miR-451a. Functional experiments demonstrated that the knockdown of miR-451a or overexpression of CAV1 could promote cell proliferation, inhibit apoptosis, and alleviate G0-G1-phase arrest while enhancing fatty acid β-oxidation. In vivo experiments further confirmed that the SNHG15/miR-451a/CAV1 axis affected gastric cancer oxaliplatin resistance by regulating fatty acid β-oxidation. This study revealed that SNHG15 inhibits miR-451a to upregulate CAV1 expression, thereby regulating fatty acid β-oxidation and influencing gastric cancer oxaliplatin resistance, providing new biomarkers and potential therapeutic targets for gastric cancer oxaliplatin resistance.