Abstract
BackgroundGrowing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD).MethodsThe expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models.ResultsST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis.ConclusionsST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.
Highlights
Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA
LncRNA ST7‐AS1 is up‐regulated in lung adenocarcinoma (LUAD) tissues and cells, and associated with worse overall survival of cancer patients Minimal information is available for the clinical or biological importance of ST7-AS1 in LUAD
We examined its expression in a panel of five different LUAD cell lines: NCI-H1975, PC-9, A549, NCI-H1299, and CALU-3
Summary
Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). Little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Understanding mechanisms underlying LUAD carcinogenesis and metastasis including EMT will aid the development of novel, effective therapies for LUAD patients. LncRNAs present diverse biological functions and work within the cells to regulate different processes through myriad molecular mechanisms [8]. Emerging evidence suggests that aberrant lncRNAs participate in LUAD development and progression [9]. Identifying molecular mechanisms of LUAD-associated lncRNAs is of great significance to better understand cancer progression and establish effective treatment of LUAD. Recent studies suggest that ST7-AS1 is an oncogenic lncRNA in both gastric cancer and laryngeal squamous cell carcinoma (LSCC) [11, 12]. Little is known on the clinical status, biological activities, or molecular mechanisms of ST7AS1 in LUAD
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