Oncogenic gene RGC‐32 is a direct target of miR‐26b and facilitates tongue squamous cell carcinoma aggressiveness through EMT and PI3K/AKT signalling

Abstract

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. Significance of the study: We first uncovered that Response Gene to Complement-32 played a significantly pro-tumorigenic role in tongue squamous cell carcinoma (TSCC), which was closely regulated by downregulation of miR-26b and activations of epithelial-mesenchymal transition process and PI3K/AKT signalling. These findings contribute to better understand the molecular mechanism in carcinogenesis of TSCC, and shed some light on promising strategy for TSCC therapeutics.

Acteoside protects retinal ganglion cells from experimental glaucoma by activating the PI3K/AKT signaling pathway via caveolin 1 upregulation

“…An aberrantly activated or inactivated PI3K/ AKT signaling pathway has been identified in a variety of human diseases (18). Additionally, researches have shown that the PI3K/AKT signaling pathway is involved in controlling proliferation, apoptosis, and autophagy of RGCs (19)(20)(21). Notably, the PI3K/AKT signaling pathway plays an important role in preventing glaucomatous injury-induced loss of RGCs (22).…”

Transient receptor potential canonical 1 is a candidate treatment target for tongue squamous cell carcinoma by inhibiting growth and invasion through phosphatidylinositol 3-kinase and protein kinase B pathway

“…Over several decades, PI3K/AKT pathway in TSCC has attracted a lot of attention from oncology researchers. For instance, it has been shown that the activation of PI3K/AKT signaling facilitates TSCC progression [25]; furthermore, the activation of the PI3K/AKT pathway is able to promote proliferation, migration, and invasion but inhibit apoptosis in TSCC cells [26]. Importantly, previous studies have proposed that TRPC1 is able to modulate PI3K/AKT pathway to regulate tumor progression in several malignancies [14,15,17].…”

Smoothened mediates medaka spermatogonia proliferation via Gli1–Rgcc–Cdk1 axis

“…A large number of stimuli such as transforming growth factor [54], steroid hormones [55], and serum [56] are able to regulate the expression of RGCC. In tongue squamous cell carcinoma (TSCC), RGCC has a tumor-promoting effect, and its knock-down promotes cell apoptosis; furthermore, it can regulate the proliferation, trans-migration, and invasion of TSCC cells through EMT and PI3K/AKT signaling pathways [57]. In the developing mammalian neocortex, RGCC is exclusively expressed in neural stem cells (NSCs); its deficiency disrupts the cell cycle and spindle orientation of NSCs, which may lead to cell pre-differentiation and exhaustion of the NSCs pool [58].…”