Oncotarget

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MicroRNA-542-3p inhibits oral squamous cell carcinoma progression by inhibiting ILK/TGF-β1/Smad2/3 signaling

Bin Qiao _, Jing-Hua Cai, Alfred King-Yin Lam and Bao-Xia He

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Oncotarget. 2017; 8:70761-70776. https://doi.org/10.18632/oncotarget.19986

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Abstract

Bin Qiao1,*, Jing-Hua Cai1,*, Alfred King-Yin Lam1,2 and Bao-Xia He3

1Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China

2Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast 4222, Australia

3Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital, Zhengzhou 450003, P.R. China

*These authors shared the co-first author

Correspondence to:

Bin Qiao, email: [email protected]

Bao-Xia He, email: [email protected]

Keywords: oral squamous cell carcinoma stem-like cells, SCC-9 cell line, microRNA-542-3p, integrin-linked kinase, TGF-β1/Smads signaling pathway

Received: March 15, 2017    Accepted: July 19, 2017    Published: August 07, 2017

ABSTRACT

In this study, we investigated the effects of microRNA-542-3p (miR-542-3p) on ILK/TGF-β1/Smad2/3 signaling and oral squamous cell carcinoma (OSCC) progression. Levels of miR-542-3p were lower in OSCC tissues (n=108) than adjacent normal tissues, whereas levels of ILK, TGF-β1 and Smad2/3 were higher. Patients with undifferentiated tumors, advanced TNM stage and lymph node metastasis showed low miR-542-3p levels. This was accompanied by high ILK expression and poor survival. Dual luciferase reporter assays of SCC-9 cells showed that miR-542-3p inhibited ILK gene expression by binding to its 3’UTR at 233-240 bp. SCC-9 cells transfected with miR-542-3p mimics exhibited elevated miR-542-3p and decreased ILK, TGF-β1 and Smad2/3 expression. They also showed reduced self-renewal (fewer CD44+ cells and tumor-spheres), invasiveness, migration, proliferation and survival. Conversely, miR-542-3p inhibitors promoted increased self-renewal (more CD44+ cells and tumor-spheres), invasiveness, migration, proliferation and survival. In xenograft experiments with nude mice, SCC-9 cells transfected with miR-542-3p mimics or siRNA-ILK yielded tumors with smaller volumes and weights than control tumors. These results demonstrate that miR-542-3p is a tumor suppressor that inhibits ILK/TGF-β1/Smad2/3 signaling, thereby inhibiting OSCC progression.


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