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

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-offunction 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.

Circ_0000140 restrains the proliferation, metastasis and glycolysis metabolism of oral squamous cell carcinoma through upregulating CDC73 via sponging miR-182-5p

“…In vivo experiments, we also proved that it could inhibit the tumor growth of OSCC. All data was similar with the results of Peng et al [14]. Further experiments showed that circ_0000140 could absorb miR-182-5p to regulate CDC73 expression.…”

“…f, g The CDC73 protein level in CAL-27 and SCC-4 cells was detected by WB analysis to evaluate the circ_0000140 and miR-182-5p expression on CDC73 expression. ** P < 0.01 expression in OSCC patients [13,14]. We also discovered that circ_0000140 had a decreased expression in OSCC, and it was a stable cyclic transcript and mainly located in the cytoplasm.…”

“…Circ_0000140 is a newly discovered circRNA with significantly low expression in OSCC patients [13]. A recent study had shown that low circ_0000140 expression was significantly associated with the poor prognosis in OSCC patients and could function as a potential biomarker for OSCC [14]. Therefore, circ_0000140 might be an important target for the treatment of OSCC, and its role and mechanism in the progression of OSCC deserved further investigation.…”

LncRNA MNX1-AS1 promotes progression of intrahepatic cholangiocarcinoma through the MNX1/Hippo axis

“…Once the Hippo pathway is inactivated, Yesassociated protein (YAP) and Tafazzin (TAZ) translocated into the nucleus to promote cell proliferation 60 . Numerous studies have also reported that the Hippo pathway participated in the progression of various malignancies 59,[61][62][63][64] .…”

The Research Progression and Clinical Significance of Circular RNAs in Head and Neck Cancers

“…Functionally, the expression of circ-0000140 can suppress cell proliferation, migration, and invasion, as well as facilitate cell apoptosis in vitro. Mechanistically, circ-0000140 enhances the expression of miR-31 and its target gene LATS2 by “sponging” miR-31, which suppresses the aggressive biological behavior of OSCC [ 30 ]. Su et al's study characterized hsa_circ_0005379 by using high-throughput transcriptome sequencing technology.…”