MiR-1290 promotes lung adenocarcinoma cell proliferation and invasion by targeting SOCS4.

Xuelian Xiao,Shiyang Pan,Dongping Mo,Daheng Yang,Xue Gong,Jian Xu

doi:10.18632/oncotarget.24046

Xuelian Xiao, Shiyang Pan + Show 4 more

Open Access

https://doi.org/10.18632/oncotarget.24046

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Journal: Oncotarget	Publication Date: Jan 8, 2018
Citations: 23	License type: cc-by

Affiliation: Jiangsu Province Hospital

Abstract

miRNAs play important roles in lung adenocarcioma (LADC) progression. We previously found that miR-1290 expression was upregulated in LADC tissue and serum samples from patients with LADC, and correlated with prognosis. However, the biological role of miR-1290 in LADC and mechanism of such role are poorly understood. Here, we found that miR-1290 overexpression promoted LADC cell proliferation, cell cycle progression and invasion, while suppressing cell apoptosis in vitro. Furthermore, miR-1290 promoted tumor growth, invasion and metastasis in vivo. miR-1290 downregulated suppressor of cytokine signaling 4 (SOCS4) at both the mRNA and protein levels by targeting SOCS4. Reduced SOCS4 level reversed the inhibitory effect of miR-1290 downregulation on cell proliferation and invasion. miR-1290 activated the JAK/STAT3 and PI3K/AKT signaling pathways by targeting SOCS4. An inverse correlation was observed between miR-1290 and SOCS4 expression in LADC tissues. Clinicopathological characteristics analysis showed that SOCS4 expression was negatively associated with higher clinical stage and lymph node metastasis. These observations suggest that miR-1290 promotes LADC cell proliferation and invasion by targeting SOCS4.

Highlights

Lung cancer is the leading cause of cancer mortality worldwide, and lung adenocarcinoma (LADC) accounts for more than 40%–4 5% of lung cancer cases [1, 2]
These findings inspired us to investigate the biological functions of miR-1290 in LADC. qRT-PCR analysis showed that miR-1290 levels were significantly higher in A549 and SPC-A1 cells than that in BEAS-2B cells (Figure 1A)
suppressor of cytokine signaling 4 (SOCS4) silencing reversed the negative effect of miR-1290 downregulation on cell proliferation and invasion (Figure 4E, 4F). These results indicated that miR-1290 enhanced LADC cell proliferation and invasion by targeting SOCS4

Summary

INTRODUCTION

Lung cancer is the leading cause of cancer mortality worldwide, and lung adenocarcinoma (LADC) accounts for more than 40%–4 5% of lung cancer cases [1, 2]. Rapid tumor proliferation and lethal distant metastasis are mainly responsible for failure of therapy and poor prognosis. A better understanding of the molecular mechanisms underlying tumor origins and progression would contribute to cancer diagnosis and therapy. Increasing evidence has emerged that miRNAs participate in various biological processes in tumors, including cell proliferation [6], apoptosis [7], invasion and metastasis [8]. Elucidation of the role of miRNAs in cancer can give new perspectives to cancer diagnosis and therapy [11, 12]. Expression of many miRNAs is disrupted in LADC [13], and accumulating evidence has validated a potential role of miRNA in LADC diagnosis and therapy [14]. LADC and the mechanisms of such effects are poorly understood

RESULTS

DISCUSSION

MATERIALS AND METHODS