The long non-coding RNA rhabdomyosarcoma 2-associated transcript exerts anti-tumor effects on lung adenocarcinoma via ubiquitination of SOX9

Abstract

Background: Long non-coding RNAs (lncRNAs) play an important role in the post-translational modification of proteins, but the importance of lncRNAs in protein ubiquitination remains unclear. This study investigated to role of the lncRNA rhabdomyosarcoma 2-associated transcript (RMST) in lung adenocarcinoma (LUAD).Methods: The expression of RMST was analyzed in LUAD samples and normal lung tissues using data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) public databases.Colony formation and transwell assays were used to determine the anti-tumor effects of RMST in human LUAD progression. RNA pull-down assays, RNA immunoprecipitation assays, and mass spectrometry were used to determine the mechanisms by which RMST induces the ubiquitination of SRY-box transcription factor 9 (SOX9). Furthermore, animal models were used to determine the effects of RMST on LUAD tumorigenicity in vivo.Results: Compared with normal tissues, RMST expression was significantly downregulated in LUAD samples. This abnormal expression of RMST led to significant changes in the proliferation and migration of LUAD cells both in vitro and in vivo. The experiments demonstrated that RMST binds directly to the SOX9 protein, resulting in the ubiquitination of SOX9 and this was mediated by F-box and WD repeat domaincontaining 7 (FBW7). Clinically, RMST expression was shown to be positively correlated with the overall survival of LUAD patients.Conclusions: These findings revealed that RMST suppressed the SOX9 signaling pathway to inhibit LUAD growth and metastasis. The RMST-induced ubiquitination of SOX9 via FBW7 may be a potential therapeutic target for the treatment of patients with LUAD.

The Risk Model Based on the Three Oxidative Stress-Related Genes Evaluates the Prognosis of LAC Patients

“…Lung adenocarcinoma has a high incidence and mortality rates [ 7 , 9 , 15 , 20 ]. At present, the prognosis of LAC patients is significantly poor.…”

Differential lncRNA/mRNA expression profiling and ceRNA network analyses in amniotic fluid from foetuses with ventricular septal defects

“…In the past few years, several ncRNA-based drugs have been in phase II or III clinical development. Most of these drugs regulate the expression of downstream genes by mimicking or antagonizing the function of ncRNA to achieve therapeutic effects ( Pei, Zhou & Liu, 2022 ). For example, an intravenous injection of a miR-378 mimic prevents excessive myocardial fibrosis in a mouse model of transverse aortic constriction ( Yuan et al, 2018 ).…”

Cooperative effects of oocytes and estrogen on the forkhead box L2 expression in mural granulosa cells in mice

“…The translation of Sox9 mRNA is controlled by the mechanistic/mammalian target of rapamycin (mTOR) signaling through the inhibition of the Eukaryotic translation initiation factor 4E-binding proteins in mesenchymal stem cells in mice 41 . Moreover, long non-coding RNAs are also involved in the regulation of SOX9 protein levels in chondrocyte differentiation and in lung adenocarcinoma 42,43 . Therefore, similar mechanisms may be present and prevent an increase in SOX9 protein levels in murine MGCs.…”