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.

• Authors: Zhong-Heng Yang, Juan Li, Wei-Zhi Chen, Fan-Shuang Kong
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 38 Issue 7 Pg. 943-954 (Oct 2020) ISSN: 1099-0844 [Electronic] England
• PMID: 32325539 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Antagomirs
• Cadherins
• Cell Cycle Proteins
• MIRN26A microRNA, human
• MicroRNAs
• Muscle Proteins
• Nerve Tissue Proteins
• RGCC protein, human
• RNA, Small Interfering
• Proto-Oncogene Proteins c-akt

Topics

• Antagomirs (metabolism)
• Cadherins (metabolism)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Cycle Proteins (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Humans
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Muscle Proteins (antagonists & inhibitors, genetics, metabolism)
• Nerve Tissue Proteins (antagonists & inhibitors, genetics, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Signal Transduction
• Tongue Neoplasms (metabolism, pathology)
• Up-Regulation