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. 2018 Oct;14(6):1289-1297.
doi: 10.5114/aoms.2017.72220. Epub 2017 Dec 13.

PAQR3 inhibits proliferation via suppressing PI3K/AKT signaling pathway in non-small cell lung cancer

Xiaohui Li  1 , Mengfei Li  1 , Dong Chen  1 , Gongning Shi  1 , Hui Zhao  1
Affiliations

PAQR3 inhibits proliferation via suppressing PI3K/AKT signaling pathway in non-small cell lung cancer

Xiaohui Li et al. Arch Med Sci. 2018 Oct.

Abstract

Introduction: Lung cancer is the leading cause of cancer-related death worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. PAQR (progestin and adipoQ receptor family) 3, a Golgi-anchored membrane protein, has been demonstrated to act as a tumor suppressor in multiple cancers. However, the expression and role of PAQR3 have never been explored in NSCLC. The purpose of this study was to investigate the expression and role of PAQR3 in NSCLC.

Material and methods: Expression of PAQR3 at mRNA and protein levels was determined by qRT-PCR and western blot, respectively. Cell proliferation was analyzed by MTT assay. Apoptosis and cell cycle distribution were evaluated by flow cytometry.

Results: The expression of PAQR3 was downregulated in NSCLC tissue samples and cell lines at both mRNA and protein levels (p < 0.05). Overexpression of PAQR3 significantly inhibited cell proliferation, induced apoptosis and promoted cell cycle arrest at G0/G1 phase in NSCLC cell lines (p < 0.05). In contrast, knockdown of PAQR3 showed a reverse effect on NSCLC cells (p < 0.05). Moreover, PAQR3 may exert its tumor suppressive roles via suppressing the PI3K/AKT signaling pathway in NSCLC.

Conclusions: Our findings suggest that PAQR3 is a tumor suppressor in the development of NSCLC and may serve as a novel therapeutic target in the treatment of patients with NSCLC.

Keywords: NSCLC; PAQR3; PI3K/AKT; proliferation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PAQR3 was down-regulated in NSCLC tissues and cell lines. A – PAQR3 mRNA level in CC tissues and the matched normal tissues as determined by qRT-PCR. B – Representative images of the PAQR3 protein expression in NSCLC tissues and the matched normal tissues as detected by western blot. C – PAQR3 mRNA level in NSCLC cell lines (SK-MES-1, A549, SPCA-1 and H1229) and the non-tumorous human bronchial epithelium cell line BEAS-2B as determined by qRT-PCR. D – PAQR3 protein expression in NSCLC cell lines and BEAS-2B cells detected by western blot Data are expressed as mean ± SD. *P < 0.05.
Figure 2
Figure 2
Overexpression of PAQR3 inhibited NSCLC cell proliferation. A, B – mRNA and protein levels of PAQR3 in NSCLC cell lines A549 and H1299 following pcDNA3.1-PAQR3 plasmid or empty vector transfection. C, D – Cell proliferation of NSCLC cells as analyzed by MTT assay after PAQR3 overexpression. E, F – Cell apoptosis of NSCLC cells as measured by flow cytometry after PAQR3 overexpression. G, H – Cell cycle distribution of NSCLC cells as assessed by flow cytometry after PAQR3 overexpression Data are expressed as mean ± SD. *P < 0.05.
Figure 2
Figure 2
Overexpression of PAQR3 inhibited NSCLC cell proliferation. A, B – mRNA and protein levels of PAQR3 in NSCLC cell lines A549 and H1299 following pcDNA3.1-PAQR3 plasmid or empty vector transfection. C, D – Cell proliferation of NSCLC cells as analyzed by MTT assay after PAQR3 overexpression. E, F – Cell apoptosis of NSCLC cells as measured by flow cytometry after PAQR3 overexpression. G, H – Cell cycle distribution of NSCLC cells as assessed by flow cytometry after PAQR3 overexpression Data are expressed as mean ± SD. *P < 0.05.
Figure 3
Figure 3
Knockdown of PAQR3 promoted NSCLC cell proliferation. A, B – mRNA and protein levels of PAQR3 in NSCLC cell lines A549 and H1299 following PAQR3 knockdown. C, D – Cell proliferation of NSCLC cells as analyzed by MTT assay after PAQR3 knockdown. E, F – Cell apoptosis of NSCLC cells as measured by flow cytometry after PAQR3 knockdown. G, H – Cell cycle distribution of NSCLC cells as assessed by flow cytometry after PAQR3 knockdown Data are expressed as mean ± SD. *P < 0.05.
Figure 3
Figure 3
Knockdown of PAQR3 promoted NSCLC cell proliferation. A, B – mRNA and protein levels of PAQR3 in NSCLC cell lines A549 and H1299 following PAQR3 knockdown. C, D – Cell proliferation of NSCLC cells as analyzed by MTT assay after PAQR3 knockdown. E, F – Cell apoptosis of NSCLC cells as measured by flow cytometry after PAQR3 knockdown. G, H – Cell cycle distribution of NSCLC cells as assessed by flow cytometry after PAQR3 knockdown Data are expressed as mean ± SD. *P < 0.05.
Figure 4
Figure 4
PAQR3 may exert its tumor suppressive roles via suppressing PI3K/AKT signaling pathway in NSCLC. A – Protein expression of PI3K and AKT and phosphorylated PI3K and AKT in A549 cells following PAQR3 overexpression. Relative quantities are shown. B – Protein expression of PI3K and AKT and phosphorylated PI3K and AKT in H1299 cells following PAQR3 overexpression. Relative quantities are shown
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