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Cell Death Dis ; 11(2): 112, 2020 02 10.
Article in English | MEDLINE | ID: mdl-32041942

ABSTRACT

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.


Subject(s)
Cell Movement , Cell Proliferation , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Mouth Neoplasms/metabolism , Protein Serine-Threonine Kinases/metabolism , RNA, Circular/metabolism , Squamous Cell Carcinoma of Head and Neck/metabolism , Animals , Apoptosis , Cell Line, Tumor , Female , Hippo Signaling Pathway , Humans , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Male , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Middle Aged , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Neoplasm Metastasis , RNA, Circular/genetics , Signal Transduction , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/secondary
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