2. Academic Validation
  3. LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2

LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2

  • Cell Death Dis. 2022 Nov 23;13(11):987. doi: 10.1038/s41419-022-05436-x.
Qiuming He # 1 2 3 4,  Chaogang Yang # 1 2 3 4,  Zhenxian Xiang # 1 2 3 4,  Guoquan Huang 1 2 3 4,  Haitao Wu 1 2 3 4,  Tingna Chen 1 2 3 4,  Rongzhang Dou 1 2 3 4,  Jialing Song 1 2 3 4,  Lei Han 1 2 3 4,  TianTian Song 1 2 3 4,  Shuyi Wang 5 6 7 8,  Bin Xiong 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 2 Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 3 Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China.
  • 4 Hubei Cancer Clinical Study Center, Wuhan, 430071, China.
  • 5 Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected].
  • 6 Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected].
  • 7 Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China. [email protected].
  • 8 Hubei Cancer Clinical Study Center, Wuhan, 430071, China. [email protected].
  • 9 Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected].
  • 10 Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected].
  • 11 Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China. [email protected].
  • 12 Hubei Cancer Clinical Study Center, Wuhan, 430071, China. [email protected].
  • # Contributed equally.
PMID: 36418856 DOI: 10.1038/s41419-022-05436-x
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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