CircZNF236 facilitates malignant progression in oral squamous cell carcinoma by sequestering miR-145-5p

Abstract

BackgroundA number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC). MethodsWe rst examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and ow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumour domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. ResultsOSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF2361 levels in patients with OSCC correlated with a poor prognosis.CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression. ConclusionCircZNF236 modulates OSCC via an miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.

Differential Expression of MicroRNA MiR-145 and MiR-155 Downstream Targets in Oral Cancers Exhibiting Limited Chemotherapy Resistance

“…The importance of miR-145 suppression becomes apparent as more and more overlapping mechanisms to suppress miR-145 activity are discovered, including the activity of circular RNAs, such as circ_ZNF236, circ_005063, and circ_000199 [56,57]. This research has demonstrated that other circular RNAs such as circ_GOLPH3 and circ_0001461 function to inhibit miR-145 as well as to inhibit additional downstream targets, such as KDM2 and NFkB [58,59].…”

Circular RNAs in Breast Cancer: An Update

“…Hsa_circ_0014130 was found to exert oncogenic effects in bladder cancer by upregulation of KCNJ12 expression via acting as a miR-132-3p sponge [30]. CircZNF236 was observed to enhance oral squamous cell carcinoma (OSCC) development through sponging miR-145-5p and consequently boosting MBTD1 expression [31].…”