Journal Article

circRNA_0000140 suppresses oral squamous cell carcinoma growth and metastasis by targeting miR-31 to inhibit Hippo signaling pathway

Xu, Pu, Fan, Hui, Peng, Qiu-Shi, Zhang, Wen-Bai, Cheng, Ya-Nan, Mao, Qiu-Hua

2020

Overview

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and has a poor prognosis. Circular RNA (circRNA) has been increasingly recognized as a crucial contributor to carcinogenesis. circRNA_0000140 has been aberrantly expressed in OSCC, but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, actinomycin D, and RNase R treatments were used to confirm head-to-tail junction sequences and the stability of circ_0000140. In vitro cell activities, including proliferation, migration, invasion, and apoptosis, were determined by colony formation, transwell, and flow cytometry assays. The expression levels of circ_0000140, Hippo signaling pathway, and serial epithelial–mesenchymal transition (EMT) markers were measured by quantitative real-time PCR, western blotting, immunofluorescence, and immunohistochemistry. Dual luciferase reporter assays and Argonaute 2-RNA immunoprecipitation assays were performed to explore the interplay among circ_0000140, miR-31, and LATS2. Subcutaneous tumor growth was observed in nude mice, in which in vivo metastasis was observed following tail vein injection of OSCC cells. circ_0000140 is derived from exons 7 to 10 of the KIAA0907 gene. It was down-regulated in OSCC tissues and cell lines, and correlated negatively with poor prognostic outcomes in OSCC patients. Gain-of-function experiments demonstrated that circ_0000140 enhancement suppressed cell proliferation, migration, and invasion, and facilitated cell apoptosis in vitro. In xenograft mouse models, overexpression of circ_0000140 was able to repress tumor growth and lung metastasis. Furthermore, mechanistic studies showed that circ_0000140 could bind with miR-31 and up-regulate its target gene LATS2 , thus affecting OSCC cellular EMT. Our findings demonstrated the roles of circ_0000140 in OSCC tumorigenesis as well as in metastasis, and circ_0000140 exerts its tumor-suppressing effect through miR-31/LATS2 axis of Hippo signaling pathway in OSCC.

• Publisher: Nature Publishing Group UK,Springer Nature B.V
• Subject: 631/67/1665 / 692/699/67 / Animal models / Animals / Antibodies / Apoptosis / Argonaute 2 protein / Biochemistry / Biomedical and Life Sciences / Carcinogenesis / Cell Biology / Cell Culture / Cell Line, Tumor / Cell migration / Cell Movement / Cell Proliferation / Circular RNA / Exons / Female / Flow cytometry / Humans / Immunofluorescence / Immunohistochemistry / Immunology / Immunoprecipitation / Kinases / Life Sciences / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - secondary / Male / Mesenchyme / Metastases / Metastasis / Mice, Inbred BALB C / Mice, Nude / MicroRNAs - genetics / MicroRNAs - metabolism / Middle Aged / Mouth Neoplasms - genetics / Mouth Neoplasms - metabolism / Mouth Neoplasms - pathology / Neoplasm Metastasis / Oral cancer / Oral squamous cell carcinoma / Protein-Serine-Threonine Kinases - metabolism / Ribonucleic acid / RNA / RNA, Circular - genetics / RNA, Circular - metabolism / Signal Transduction / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck - genetics / Squamous Cell Carcinoma of Head and Neck - metabolism / Squamous Cell Carcinoma of Head and Neck - secondary / Tumorigenesis / Western blotting / Xenografts