LINC00924-induced Fatty Acid Metabolic Reprogramming Facilitates Gastric Cancer Peritoneal Metastasis Via HnRNPC-regulated Alternative Splicing of Mnk2

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Nov 23

PMID 36418856

Authors

Qiuming He

Chaogang Yang

Zhenxian Xiang

Guoquan Huang

Haitao Wu

Tingna Chen

Rongzhang Dou

Jialing Song

Lei Han

Tiantian Song

Shuyi Wang

Bin Xiong

Affiliations

Soon will be listed here.

Abstract

The molecular mechanism underlying gastric cancer (GC) peritoneal metastasis (PM) remains unclear. Here, we identified LINC00924 as a GC PM-related lncRNA through Microarray sequencing. LINC00924 was highly expressed in GC, and its high expression is associated with a broad range of PM. Via RNA sequencing, RNA pulldown assay, mass spectrometry, Seahorse, Lipidomics, spheroid formation and cell viability assays, we found that LINC00924 promoted fatty acid (FA) oxidation (FAO) and FA uptake, which was essential for matrix-detached GC cell survival and spheroid formation. Regarding the mechanism, LINC00924 regulated the alternative splicing (AS) of Mnk2 pre-mRNA by binding to hnRNPC. Specifically, LINC00924 enhanced the binding of hnRNPC to Mnk2 pre-mRNA at e14a, thus downregulating Mnk2a splicing and regulating the p38 MAPK/PPARα signaling pathway. Collectively, our results demonstrate that LINC00924 plays a role in promoting GC PM and could serve as a drug target.

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