POM121 promotes proliferation and metastasis in non-small-cell lung cancer through TGF-β/SMAD and PI3K/AKT pathways

Article type: Research Article

Authors: Guan, Lirong^{a; 1} | Zhang, Lingli^{b; 1} | Wang, Tengqi^c | Jia, Lizhou^d | Zhang, Ning^d | Yan, Huishan^e | Zhao, Kun^{f; *}

Affiliations: [a] Emergency Center, Bayannur Hospital, Bayannur, Inner Mongolia, China | [b] Department of Ophthalmology, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia, China | [c] Cancer Center, Banyannur Hospital, Bayannur, Inner Mongolia, China | [d] Central Laboratory, Bayannur Hospital, Bayannur, Inner Mongolia, China | [e] Baotou Medical College, Baotou, Inner Mongolia, China | [f] Department of Oncology, Huaian Hospital of Huaian City, Huaian, Jiangsu, China

Correspondence: [*] Corresponding author: Kun Zhao, Department of Oncology, Huaian Hospital of Huaian, No. 161 Zhenhuailou East Road, Huaian, Jiangsu 223200, China. E-mail: [email protected].

Note: [1] Contributed equally.

Abstract: BACKGROUND: Nuclear pore membrane protein 121 (POM121) is a novel biomarker involved in tumorigenesis and metastasis. However, little is known about the role of POM121 in non-small-cell lung cancer (NSCLC). OBJECTIVE: The aim of this study was to detect the expression of POM121 in NSCLC and its relationship with clinicopathologic feature and cell biological behavior, and explore the underlying mechanisms. METHODS: The expression of POM121 in NSCLC tissues and para-carcinoma tissues was compared by quantitative real-time PCR and immunohistochemistry analysis. The relationship between POM121 protein and clinicopathological characteristics in NSCLC was investigated. Roles of POM121 in NSCLC cells were investigated by CCK-8 assay, clone formation assay, transwell migration and invasion assay, and in vivo experiments. Variations of signaling pathways were determined by qRT-PCR and Western blot. RESULTS: The POM121 expression in NSCLC tissues was significantly higher than that in para-carcinoma tissues, both at the mRNA and protein level. The POM121 expression was related to sex, advanced differentiation, tumor diameter, lymph node metastases, distant metastases, American Joint Committee on Cancer (AJCC) stage, venous invasion, and perineural invasion in NSCLC. Kaplan-Meier analysis indicated that NSCLC patients with high POM121 expression had poor overall survival. Downregulation of POM121 inhibited cell proliferation, clone formation, migration and invasion. TGF-β/SMAD and PI3K/AKT pathways were involved in POM121-induced functional changes in NSCLC cells. CONCLUSION: POM121 plays an oncogenic role in NSCLC through TGF-β/SMAD and PI3K/AKT pathways. POM121 expression is a potential independent prognostic factor for NSCLC.

Keywords: POM121, non-small-cell lung cancer, prognosis, TGF-β/SMAD, PI3K/AKT

DOI: 10.3233/CBM-210001

Journal: Cancer Biomarkers, vol. 32, no. 3, pp. 293-302, 2021