期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 23, 期 -, 页码 1288-1303出版社
CELL PRESS
DOI: 10.1016/j.omtn.2021.02.003
关键词
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资金
- National Natural Science Foundation of China [81871902, 81772509, 81772518]
- Multicenter Clinical Trial of Shanghai Jiao Tong University School of Medicine [DLY201602]
- Shanghai Municipal Education CommissionGaofeng Clinical Medicine Grant Support [20152505]
- Shanghai Anticancer Association [SACA-CY19C10]
The study revealed that lnc-CTSLP4 is significantly downregulated in gastric cancer tumor tissues, and by interacting with proteins and recruiting E3 ubiquitin ligase ZFP91, it inhibits the metastatic potential of GC cells.
Tumor metastasis is a crucial impediment to the treatment of gastric cancer (GC), and the epithelial-to-mesenchymal transition (EMT) program plays a critical role for the initiation of GC metastasis. Thus, the aim of this study is to investigate the regulation of lnc-CTSLP4 in the EMT process during GC progression. We found that lnc-CTSLP4 was significantly downregulated in GC tumor tissues compared with adjacent non-tumor tissues, and its levels in GC tumor tissues were closely correlated with tumor local invasion, TNM stage, lymph node metastasis, and prognosis of GC patients. Loss-and gain-of-function assays indicated that lnc-CTSLP4 inhibited GC cell migration, invasion, and EMT in vitro, as well as peritoneal dissemination in vivo. Mechanistic analysis demonstrated that lnc-CTSLP4 could bind with Hsp90 alpha/heteroge-neous nuclear ribonucleoprotein AB (HNRNPAB) complex and recruit E3-ubiquitin ligase ZFP91 to induce the degradation of HNRNPAB, thus suppressing the transcriptional activation of Snail and ultimately reversing EMT of GC cells. Taken together, our results suggest that lnc-CTSLP4 is significantly downregulated in GC tumor tissues and inhibits metastatic potential of GC cells by attenuating HNRNPAB-dependent Snail transcription via interacting with Hsp90 alpha and recruiting E3 ubiquitin ligase ZFP91, which shows that lnc-CTSLP4 could serve as a prognostic biomarker and therapeutic target for metastatic GC.
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