LncRNA SNHG20 enhances the progression of oral squamous cell carcinoma by regulating the miR-29a/DIXDC1/Wnt regulatory axis.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) comprises approximately ~90% of all oral malignancies and exhibits a significant mortality rate worldwide. Although the dysregulation of small nucleolar RNA host gene 20 (SNHG20) participates in the development of multiple malignancies, the molecular mechanisms underlying its regulation of OSCC progression remain to be fully elucidated. PATIENTS AND METHODS: The expression levels of SNHG20, microRNA-29a (miR-29a), and Disheveled-Axin Domain Containing 1 (DIXDC1) were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The protein expression levels of DIXDC1 and ß-catenin were measured by Western blotting. In addition, MTT assay was performed to measure the cell proliferation ability in SCC9 and SCC15 cells. Cell migration and invasion abilities were measured by wound healing assay and transwell assay, respectively. The cell apoptosis was assessed by flow cytometry assay. Besides, Luciferase reporter assay was employed to examine the interrelation between miR-29a and SNHG20 or DIXDC1. RESULTS: It was demonstrated that SNHG20 and DIXDC1 were significantly upregulated in OSCC tissues and cell lines, while miR-29a was markedly downregulated. Moreover, the high expression of SNHG20 was found to predict a lower survival rate in OSCC patients. In addition, loss-of-function experiments demonstrated that SNHG20 knockdown inhibited the development and progression of OSCC, whereas the miR-29a inhibitor significantly abolished the effect of SNHG20 depletion on OSCC progression by directly binding to SNHG20. DIXDC1 was shown to enhance si-SNHG20 and miR-29a mimic-attenuated cell viability, migration, and invasion by directly binding to miR-29a. Furthermore, it was also found that DIXDC1 activated Wnt signaling in OSCC cells. CONCLUSIONS: Our study demonstrated that SNHG20 promoted OSCC progression via the miR-29a/DIXDC1/Wnt signaling pathway, which might provide a novel theoretical basis for the treatment of OSCC.

Clostridium sporogenes delivers interleukin-12 to hypoxic tumours, producing antitumour activity without significant toxicity.

UNLABELLED: Clostridium sporogenes ATCC 3584 is an obligate anaerobe that has been reported to possess excellent tumour-targeting capacity. Here, we use Cl. sporogenes as a vector to deliver IL-12, a potent antitumour cytokine that bears numerous antitumour properties but that has limited clinical applications due to its strong toxicity when delivered systemically. In this study, Cl. sporogenes was genetically engineered to secrete murine IL-12, and its antitumour efficacy and toxicity were investigated in a murine EMT6 mammary carcinoma model. After intravenous injection, Cl. sporogenes was able to selectively settle and reproduce in the tumours without encroaching on normal tissues, resulting in a clear delay of tumour growth and a 14·3% cure rate. Importantly, the mice showed no obvious toxicity-associated side effects, such as diarrhoea and weight loss, during the treatment process. The significant antitumour efficacy and low toxicity of this treatment may be explained by the selective tumour-targeting properties of Cl. sporogenes and by the sustained release of IL-12 accompanying bacterial proliferation. This moderate local IL-12 concentration would not induce the severe response in the entire body, that is inevitable when IL-12 is administered directly. SIGNIFICANCE AND IMPACT OF THE STUDY: Interleukin-12 (IL-12) is a potent antitumour cytokine, but it is toxic when administrated systemically. This study demonstrates that murine IL-12 can be systemically delivered to hypoxic sites in solid tumours by Clostridium sporogenes, producing a clear delay in tumour growth and a 14·3% cure rate in a mouse tumour model. Importantly, there is no obvious toxicity associated with IL-12 during the treatment process. This result may be accounted for by the excellent tumour-targeting capacity of Cl. sporogenes, targeting IL-12 directly to the tumour site instead of to the entire body.