Abstract
BackgroundLong non-coding RNA (lncRNA) as a widespread and pivotal epigenetic molecule participates in the occurrence and progression of malignant tumors. DRAIC, a kind of lncRNA whose coding gene location is on 15q23 chromatin, has been found to be weakly expressed in a variety of malignant tumors and acts as a suppressor, but its characteristics and role in gastric cancer (GC) remain to be elucidated.MethodsSixty-seven primary GC tissues and paired paracancerous normal tissues were collected. Bioinformatics is used to predict the interaction molecules of DRAIC. DRAIC and NFRKB were overexpressed or interfered exogenously in GC cells by lentivirus or transient transfection. Quantitative real-time PCR (qPCR) and western blotting were used to evaluate the expression of DRAIC, UCHL5 and NFRKB. The combinations of DRAIC and NFRKB or UCHL5 and NFRKB were verified by RNA-IP and Co-IP assays. Ubiquitination-IP and the treatment of MG132 and CHX were used to detect the ubiquitylation level of NFRKB. The CCK-8 and transwell invasion and migration assays measured the proliferation, migration and invasion of GC cells.ResultsDRAIC is down-regulated in GC tissues and cell lines while its potential interacting molecules UCHL5 and NFRKB are up-regulated, and DRAIC is positively correlated with NFRKB protein instead of mRNA. Lower DRAIC and higher UCHL5 and NFRKB indicated advanced progression of GC patients. DRAIC could increase NFRKB protein significantly instead of NFRKB mRNA and UCHL5, and bind to UCHL5. DRAIC combined with UCHL5 and attenuated binding of UCHL5 and NFRKB, meanwhile promoting the degradation of NFRKB via ubiquitination, and then inhibited the proliferation and metastasis of GC cells, which can be rescued by oeNFRKB.ConclusionDRAIC suppresses GC proliferation and metastasis via interfering with the combination of UCHL5 and NFRKB and mediating ubiquitination degradation.
Highlights
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract
We analyzed the expression of Downregulated RNA in cancer (DRAIC), Ubiquitin C-terminal hydrolase L5 (UCHL5) and Nuclear factor related to kappaB binding protein (NFRKB) in gastric cancer (GC) through the TCGA database, and found that DRAIC was down-regulated in GC tissues, while both UCHL5 and NFRKB were highly expressed (Fig. 1b, c and d), which suggested that they may participate in the formation of GC
We observed that the expression of DRAIC decreased with the progression of gastric cancer (Fig. 1e), while the low expression of DRAIC and high expression of NFRKB were extremely adverse for the prognosis of GC patients (Fig. 1f and g)
Summary
Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract. The lack of specific diagnostic markers for early GC and the absence of targeting drugs contribute to poor prognosis of patients with GC. It is crucial to clarify the exact mechanism of the occurrence and development of GC and to develop new targeted drugs and diagnostic kits for improving the prognosis of GC patients. Long non-coding RNA (lncRNA) as a widespread and pivotal epigenetic molecule participates in the occurrence and progression of malignant tumors. DRAIC, a kind of lncRNA whose coding gene location is on 15q23 chromatin, has been found to be weakly expressed in a variety of malignant tumors and acts as a suppressor, but its characteristics and role in gastric cancer (GC) remain to be elucidated
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