TSPAN12 is overexpressed in NSCLC via p53 inhibition and promotes NSCLC cell growth in vitro and in vivo

Zhongwu Hu,¹ Daorong Hou,² Xiaowei Wang,³ Zhenbing You,¹ Xiufeng Cao<sup>4

1</sup>Department of Thoracic Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, China; ²Key Laboratory of Model Animal Research, Animal Core Facility of Nanjing Medical University, Nanjing, China; ³Department of Medical Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China; ⁴Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

Background: Tetraspanin 12 (TSPAN12), a member of the phylogenetically ancient tetraspanin family, is linked to impaired vascularization of the eye called familial exudative vitreoretinopathy, while the functional role of TSPAN12 in lung cancer has not been well characterized.
Results: In our study, TSPAN12 is able to regulate the growth of non-small-cell lung carcinoma (NSCLC) cells both in vitro and in vivo. TSPAN12 mRNA level was significantly increased in human NSCLC samples compared with their corresponding paracancerous histologic normal tissues. In addition, TSPAN12 expression, which is frequently upregulated in NSCLC, is inversely correlated with p53 expression. Furthermore, the expression levels of TSPAN12 were also increased in three human NSCLC cell lines compared to human bronchial epithelial (16HBE) cells. Then, we studied the effects of TSPAN12 silencing by short hairpin ribonucleic acid on NSCLC cell growth in vitro and tumorigenesis in vivo, along with the effect on the p53 pathway. Knockdown of TSPAN12 in NSCLC cells inhibited cell proliferation and colony formation. In addition, knockdown of TSPAN12 increased apoptosis in NSCLC cells. Mechanistically, TSPAN12 could modulate the expression of p53, p21, and p27 in NSCLC cells. In a tumor xenograft model, TSPAN12 silencing inhibits the tumor growth of H1299 cells.
Conclusion: Taken together, our results reveal that TSPAN12 plays an important role in NSCLC and is a potential biomarker and a promising target in the treatment of NSCLC.

Keywords: NSCLC, TSPAN12, p53, survival, cell proliferation, apoptosis