ADCY9 functions as a novel cancer suppressor gene in lung adenocarcinoma

Yijie Tang; Tianyi Wang; Anping Zhang; Jiaqi Zhu; Tingting Zhou; You-Lang Zhou; Jiahai Shi

doi:10.21037/jtd-22-1027

ADCY9 functions as a novel cancer suppressor gene in lung adenocarcinoma

J Thorac Dis. 2023 Mar 31;15(3):1018-1035. doi: 10.21037/jtd-22-1027. Epub 2023 Mar 27.

Authors

Yijie Tang^#^{1

2}, Tianyi Wang^#^{1

2}, Anping Zhang^{1

2}, Jiaqi Zhu^{1

2}, Tingting Zhou^{1

2}, You-Lang Zhou³, Jiahai Shi^{1

2

4}

Affiliations

¹ Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, China.
² Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
³ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
⁴ School of Public Health, Nantong University, Nantong, China.

^# Contributed equally.

Abstract

Background: The process of lucubrating into lung adenocarcinoma (LUAD) is of profound clinical and practical significance in improving the prognosis of LUAD patients. Multiple biomarkers are reportedly involved in the proliferation or metastasis of adenocarcinoma. However, whether the ADCY9 gene influences the development of LUAD remains unknown. Therefore, we aimed to elucidate the relationship between the expression of ADCY9 and the proliferation and migration of LUAD.

Methods: The ADCY9 gene was filtered via a survival analysis of LUAD acquired from the Gene Expression Omnibus (GEO). Then, we conducted a validation analysis and ADCY9-microRNA, microRNA-lncRNA, and ADCY9-lncRNA targeting relationship analysis through the data obtained from The Cancer Genome Atlas (TCGA) dataset. The survival curve, correlation, and prognostic analysis were implemented through bioinformatics methods. Both protein and mRNA expression levels of LUAD cell lines and LUAD patient samples (80 pairs) were detected using western blot assays and quantitative real-time polymerase chain reaction (qRT-PCR). An immunohistochemistry assay was performed to display the correlation between the expression level of the ADCY9 gene and prognosis in LUAD patients (2012-2013; n=115). Overexpression of cell lines SPCA1 and A549 were used for a series of cell function assays.

Results: Compared with the expression level in adjacent normal tissues, ADCY9 expression was downregulated in LUAD tissues. Based on the result of the survival curve analysis, high expression of ADCY9 may lead to a better prognosis and may be seen as an independent predictor for LUAD patients. High expression of ADCY9-related microRNA hsa-miR-7-5p may lead to a worse prognosis, and high expression of hsa-miR-7-5p-related lncRNAs may lead to the opposite effects. Overexpression of ADCY9 restrained the proliferation, invasion, and migration abilities of SPCA1, A549 cells.

Conclusions: Results indicate that the ADCY9 gene acts as a tumor suppressor to restrain the proliferation, migration, and invasion in LUAD and can lead to a better survival or prognosis in LUAD patients.

Keywords: ADCY9 gene; lung adenocarcinoma (LUAD); tumor migration and invasion.