LncRNA CASC19 promotes gastric cancer progression through preventing CREB1 protein ubiquitin/proteasome-dependent degradation

Shidong Wang; Chen Qiao; Jun Li; Si Liu; Peng Li

doi:10.1093/carcin/bgad001

LncRNA CASC19 promotes gastric cancer progression through preventing CREB1 protein ubiquitin/proteasome-dependent degradation

Carcinogenesis. 2023 May 27;44(3):209-220. doi: 10.1093/carcin/bgad001.

Authors

Shidong Wang^{1

2

3}, Chen Qiao^{1

2

3}, Jun Li⁴, Si Liu^{1

2

3}, Peng Li^{1

2

3}

Affiliations

¹ Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
² Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, 100050, China.
³ National Clinical Research Center for Digestive Diseases, Beijing, 100050, China.
⁴ Department of Gastroenterology, Chui Yang Liu Hospital Affiliated to Tsinghua University, Beijing, 100050, China.

PMID: 36651836
DOI: 10.1093/carcin/bgad001

Abstract

Cancer susceptibility candidate 19 (CASC19) is a novel long non-coding RNA (lncRNA) that has been reported to implicate in the development and therapeutic resistance of various cancers. However, the biological functions and the underlying mechanisms of CASC19 in gastric cancer (GC) remain unclear. In this study, GC-related lncRNAs were screened by lnCAR-database analysis. Based on Gene Expression Profiling Interactive Analysis (GEPIA) database, GC survival analysis associated with CASC19 was carried out. Quantitative real-time PCR (qRT-PCR) and chromogenic in situ hybridization were adopted to determine the expression level of CASC19. 5-ethynyl-2'-deoxyuridine (EdU) assay, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and cell cycle assay were used to measure the proliferation capabilities of GC cells. Wound healing assay, transwell migration and invasion assay were performed to detect the metastatic ability of GC cells. Furthermore, subcellular fractionation assay, mass spectrometry, RNA pull-down, RNA immunoprecipitation, western blot and protein stability assay were conducted to investigate the mechanism of CASC19 in GC. Here, we report that CASC19 exerts an oncogenic effect on GC. CASC19 was found to be elevated in GC and overexpression of CASC19 was associated with advanced TNM (tumor node metastasis) stage and poor prognosis. Functionally, CASC19 knockdown inhibited GC cells proliferation, migration and invasion, and induced cell cycle arrest. Mechanistically, CASC19 interacted with cAMP response element-binding protein 1 (CREB1) and enhanced its stability by preventing its ubiquitin/proteasome-dependent degradation. In conclusion, these findings suggest that CASC19 may act as a cancer accelerator in GC by regulating CREB1 stability and highlight CASC19 as a potential biomarker and a valuable therapeutic target for advanced GC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Cyclic AMP Response Element-Binding Protein / genetics
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs* / genetics
Proteasome Endopeptidase Complex / genetics
Proteasome Endopeptidase Complex / metabolism
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Stomach Neoplasms* / pathology
Ubiquitin / metabolism

Substances

RNA, Long Noncoding
Proteasome Endopeptidase Complex
Ubiquitin
Cyclic AMP Response Element-Binding Protein
MicroRNAs
CREB1 protein, human