Abstract
Purpose: MicroRNAs are known to regulate cellular processes in non-small cell lung cancer (NSCLC) cells and predict prognosis. However, identification of specific microRNAs in NSCLC as potential therapeutic targets is controversial. We aim to determine the clinical significance of miR-1323 in the prognosis of patients with lung cancer and the potential mechanism.Patients and methods: A bioinformatics approach was used to screen the importance microRNA in NSCLC through the online GEO database (GSE42425). The relationship between expression level of miR-1323 and overall survival of lung cancer patients was analyzed. Additionally, an independent corhort including 53 NSCLC cases that underwent resection validated the connection between miR-1323 and LUAD patients' overall survival. Next, the function of miR-1323 was studied in vitro by transient transfection. A more in-depth mechanism was studied through luciferase reporter gene experiments.Results: High miR-1323 expression correlated with poor survival in NSCLC patients (P = 0.011), and in lung adenocarcinoma (LUAD) patients (P = 0.015) based on GEO database (GSE42425). In the independent cohort based on our hospital, high miR-1323 expression was associated with LUAD patients (P = 0.025). Moreover, transfection with mimics of miR-1323 showed an increased migratory capacity in LUAD A549 and HCC827 cells. In addition, E3 ubiquitin-protein ligase Casitas B-lineage Lymphoma-b (Cbl-b) was found to be the target genes of miR-1323 and significantly down regulated after mimics of miR-1323 transfection, and high Cbl-b expression predicted better prognosis in NSCLC and LUAD (P = 0.00072 and P = 0.02, respectively).Conclusion: The miR-1323 promoted LUAD migration through inhibiting Cbl-b expression. High miR-1323 expression predicted poor prognosis in LUAD patients.
Highlights
Non-small cell lung cancer (NSCLC) is a leading cause of cancerrelated death and accounts for 80–85% of all lung cancer cases [1]
High miR-1323 expression correlated with poor survival in NSCLC patients (P = 0.011), and in lung adenocarcinoma (LUAD) patients (P = 0.015) based on GEO database (GSE42425)
In the independent cohort based on our hospital, high miR-1323 expression was associated with LUAD patients (P = 0.025)
Summary
Non-small cell lung cancer (NSCLC) is a leading cause of cancerrelated death and accounts for 80–85% of all lung cancer cases [1]. The prognosis of patients with NSCLC is very poor and the majority of patients are diagnosed at an advanced stage owing to the lack of cancer-specific symptoms. Epidermal growth factor receptor (EGFR) has emerged as a major target for NSCLC therapy, almost all patients on this treatment inevitably acquire drug resistance, but the prognosis of patients remains poor [2]. Identification of new targets in lung cancer is urgently needed. A previous study has shown that microRNAs are involved in multiple aspects of lung cancer such as cell proliferation, apoptosis, invasion, and EMT [3,4,5,6]. The survival of lung cancer patients has been predicted by a series of microRNAs such as miR-133b, miR-93-5p [7, 8]. Specific microRNAs playing a significant prognostic role in NSCLC are not determined
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