Growing data have recognized the significance of Response Gene to Complement (RGC)‐32 in numerous tumour developments. Notwithstanding, the functional role and underlying mechanism of it in tongue squamous cell carcinoma (TSCC) remain enigmatic. Here, to identify the impact of RGC‐32 in TSCC, its expression in multiple TSCC cells was measured and loss‐of‐function experiments in cell lines were performed to illuminate the function of it induced TSCC progression, via si‐RNA knockdown, CCK‐8, colony formation, wound‐healing, transwell, flow cytometry and western blot assays. To clarify potential mechanism, expressions of hallmarks in epithelial‐mesenchymal transition (EMT) process and PI3K/AKT signalling were assessed, and the upstream miR regulator of RGC‐32 was predicted and verified by applying bioinformatic approaches and dual‐luciferase reporter assay, respectively. Finally, the rescue experiments were applied to better elucidate the effect of miR‐26b/RGC‐32 axis in TSCC behaviours. As a result, RGC‐32 was upregulated in TSCC cells and knocking down of it abrogated cell proliferation, trans‐migration and invasion, whilst promoted apoptosis in TSCC, which was regulated through repressing EMT and inactivation of PI3K/AKT signalling. Subsequently, miR‐26b was predicted and identified as an upstream regulator of RGC‐32, and the pro‐tumorigenic effect of RGC‐32 was reversed by miR‐26b overexpression. Collectively, our results demonstrated that RGC‐32 facilitated TSCC progression, which was modulated by activations of PI3K/AKT pathway and EMT process, and reduction of its negative regulator of miR‐26b. These findings highlight a novel role of miR‐26b/RGC‐32 axis in TSCC and underlying mechanism, encouraging a potent usage in TSCC treatment.

中文翻译：

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致癌基因RGC-32是miR-26b的直接靶标，并通过EMT和PI3K / AKT信号传导促进舌鳞癌的侵袭性。

越来越多的数据已经认识到补体应答基因（RGC）-32在许多肿瘤发展中的重要性。尽管如此，其在舌鳞状细胞癌（TSCC）中的功能作用和潜在机制仍然是个谜。在这里，为了确定RGC-32在TSCC中的影响，测量了其在多个TSCC细胞中的表达，并通过si-RNA敲低，CCK进行了细胞系功能丧失实验以阐明其诱导TSCC进程的功能‐8，集落形成，伤口愈合，transwell，流式细胞术和蛋白质印迹分析。为了阐明潜在的机制，我们评估了上皮-间质转化（EMT）过程和PI3K / AKT信号传导中标志的表达，分别通过应用生物信息学方法和双荧光素酶报告基因测定法来预测和验证RGC-32的上游miR调节剂。最后，应用抢救实验更好地阐明了miR‐26b / RGC‐32轴在TSCC行为中的作用。结果，RGC-32在TSCC细胞中被上调，而敲除RGC-32则废除了细胞的增殖，转运和侵袭，同时促进TSCC的凋亡，这是通过抑制EMT和PI3K / AKT信号的失活来调节的。随后，miR-26b被预测并鉴定为RGC-32的上游调节物，miR-26b的过表达逆转了RGC-32的促癌作用。总的来说，我们的结果表明，RGC-32促进了TSCC的进展，这受PI3K / AKT途径和EMT过程的激活所调节，降低其miR‐26b负调节剂。这些发现突显了miR‐26b / RGC‐32轴在TSCC中的新作用及其潜在机制，从而鼓励在TSCC治疗中有效使用。