miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1.

miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention.

Jia LF ，Huang YP ，Zheng YF ，Lyu MY ，Wei SB ，Meng Z ，Gan YH ... -  《-》

[Relationships between microRNA expressions and prognosis in patients with tongue squamous cell carcinoma and the mechanisms microRNA regulating tongue squamous cell carcinoma biological behavior].

Jia LF ，Gan YH ，Yu GY 《-》

MicroRNA-137 suppresses tongue squamous carcinoma cell proliferation, migration and invasion.

Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral malignancy. Increasing evidence has shown that miRNAs play key roles in many biological processes such as cell development, invasion, proliferation, differentiation, metabolism, apoptosis and migration. qRT-PCR analysis was performed to measure miR-137 expression. CCK-8 analysis, cell colony formation, wound-healing analysis and invasion were performed to detect resultant cell functions. The direct target of miR-137 was labelled and measured by luciferase assay and Western blotting. We demonstrated that expression of miR-137 was downregulated in TSCC tissues compared to matched normal ones. miR-137 expression was downregulated in TSCC lines (SCC4, SCC1, UM1 and Cal27) compared to the immortalized NOK16B cell line and normal oral keratinocytes in culture (NHOK). In addition, we have shown that miR-137 expression was epigenetically regulated in TSCCs. Overexpression of miR-137 suppressed TSCC proliferation and colony formation. Ectopic expression of miR-137 promoted expression of the epithelial biomarker, E-cadherin, and inhibited the mesenchymal biomarker, N-cadherin, as well as vimentin and Snail expression, indicating that miR-137 suppressed TSCC epithelial-mesenchymal transition (EMT). We also showed that ectopic expression of miR-137 inhibited TSCC invasion and migration. In addition, we identified SP1 as a direct target gene of miR-137 in SCC1 cells. SP1 overexpression rescued inhibitory effects exerted by miR-137 on cell proliferation and EMT. These results indicate that miR-137 acted as a tumour suppressor in TSCC by targeting SP1.

Sun L ，Liang J ，Wang Q ，Li Z ，Du Y ，Xu X ... -  《-》

miR-34a inhibits migration and invasion of tongue squamous cell carcinoma via targeting MMP9 and MMP14.

Jia LF ，Wei SB ，Mitchelson K ，Gao Y ，Zheng YF ，Meng Z ，Gan YH ，Yu GY ... -  《PLoS One》

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

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.

Yang ZH ，Li J ，Chen WZ ，Kong FS ... -  《-》