J Cancer 2020; 11(9):2610-2620. doi:10.7150/jca.39884 This issue
1. Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China;
2. Suzhou Key Laboratory for Respiratory Diseases, Suzhou, 215006, China;
3. Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China;
4. Department of Respiratory Medicine, the First People's Hospital of Yancheng City, Yancheng, 224001, China.
*These authors contributed equally to this work.
Purpose: Lung cancer is the most common malignancy with poor 5-year survival among men and women. Previous studies have shown that CPNE1 is up-regulated in non-small cell lung cancer (NSCLC). However, whether and how CPNE1 expression varies between different subtypes of NSCLC remains less understood.
Methods: Bioinformatical analysis and GSE19188 were selected to confirm CPNE1 expression in different subtypes of NSCLC. Four microRNA prediction websites and GSE53883, GSE43000 were used to evaluate the possible targeting microRNAs. Kaplan-Meier survival curves were drawn based on Tumor Lung Bild -114 dataset using R2, UCSC Xena browser or linkedomics platform. Furthermore, we verified our prediction via qRT-PCR, and western blot and luciferase reporter assays.
Results: we demonstrated that higher CPNE1 expression was associated with poorer survival in NSCLC patients. Moreover, among the different subtypes, patients with squamous cell lung cancer (SCC) exhibited higher level of CPNE1 expression, as well as substantially poorer survival. MiR-195-5p was down-regulated in NSCLC tissues. Interestingly, SCC patients showed lower miR-195-5p expression compared to patients with lung adenocarcinoma (ADC). In addition, functional assays proved that miR-195-5p overexpression inhibited the proliferation, migration, and invasion of NSCLC-derived cells by directly targeting CPNE1. Pathway analysis showed decreased expression of p-AKT, p-Erk, and Snail after transfection with miR-195-5p mimics in both lung adenocarcinoma and squamous cell lines.
Conclusion: Our findings suggested that miR-195-5p regulation contributed to the differential expression of CPNE1 in NSCLC subtypes.
Keywords: CPNE1, non-small cell lung cancer, tumor subtype, miR-195-5p, differential expression