Tumor Suppressive Circular RNA-102450: Development of a Novel Diagnostic Procedure for Lymph Node Metastasis from Oral Cancer

Abstract

Circular RNAs (circRNAs), which form as covalently closed loop structures, have several biological functions such as regulation of cellular behavior by adsorbing microRNAs. However, there is limited information of circRNAs in oral squamous cell carcinoma (OSCC). Here, we aimed to elucidate the roles of aberrantly expressed circRNAs in OSCC. CircRNA microarray showed that circRNA-102450 was down-regulated in OSCC cells. Clinical validation of circRNA-102450 was performed using highly sensitive droplet digital PCR in preoperative liquid biopsy samples from 30 OSCC patients. Interestingly, none of 16 studied patients with high circRNA-102450 had regional lymph node metastasis (RLNM), whereas 4 of 14 studied patients (28.5%) with low expression had pathologically proven RLNM. Overexpressed circRNA-102450 significantly inhibited the tumor metastatic properties of cell proliferation, migration, and invasion. Furthermore, circRNA-102450 directly bound to, and consequently down-regulated, miR-1178 in OSCC cells. Taken together, circRNA-102450 has a tumor suppressive effect via the circRNA-102450/miR-1178 axis and may be a novel potential marker of RLNM in OSCC patients.

Synthetic Circular RNA for microRNA-1269a Suppresses Tumor Progression in Oral Squamous Cell Carcinoma

“…Therefore, novel therapeutic targets for OSCC that act at a molecular level are needed. Numerous endogenous circRNAs are gaining increasing attention in cancers [ 13 , 33 , 34 , 35 ]. Several reports [ 13 , 33 , 34 , 35 ], including our previous study [ 13 ], showed that circRNAs are involved in the progression, metastasis, and multidrug resistance of cancers, suggesting that circRNAs could be diagnostic and/or therapeutic targets for multiple cancers.…”

“…The loop structures of circRNAs confer stability and resistance to endonuclease-mediated degradation that in turn affords substantially longer circulatory half-lives relative to linear RNAs [ 12 ]. Endogenous circRNAs contain selectively conserved miR binding sites and thereby can function as efficient miR sponges that counteract miR activity [ 12 , 13 , 14 , 15 ]. Although recent research on circRNAs provided promising new insights into miR regulation [ 12 , 15 ], the construction and application of artificial synthetic circRNAs targeting specific onco-miRs remains limited.…”

Downregulation of circLPAR3 inhibits tumor progression and glycolysis by liberating miR‐144‐3p and upregulating LPCAT1 in oral squamous cell carcinoma

“…More and more research has displayed the vital roles of circRNAs in tumorigenesis and advancement, including OSCC 9 . For instance, circ‐102,450 exerts a repressive effect on OSCC cell invasion and proliferation 10 . Also, circ‐IGHG 11 and circ‐EPSTI1 12 contribute to OSCC progression through inducing epithelial‐to‐mesenchymal transition.…”

“…9 For instance, circ-102,450 exerts a repressive effect on OSCC cell invasion and proliferation. 10 Also, circ-IGHG 11 and circ-EPSTI1 12 contribute to OSCC progression through inducing epithelial-to-mesenchymal transition.…”

Nucleic Acids in Cancer Diagnosis and Therapy

“…Le et al comprehensively summarized and introduced various types of non-coding RNAs and their clinical applications in lung cancer [ 17 ]. Furthermore, the significant role of recently highlighted non-coding RNAs, including small nucleolar RNAs (snoRNAs) and circular RNAs (circRNAs), were investigated in breast cancer and oral cancer [ 18 , 19 ]. In addition, it is shown in this Special Issue that not only non-coding RNAs but also coding RNAs, including NOTCH1 mRNA, are notable prognostic markers in head and neck squamous cell carcinoma (HNSCC) [ 20 ].…”