Summary Pulpitis suppressed the level of let‐7c‐5p that promotes osteogenesis and bone formation by repressing HMGA2. In the current study, the function of let‐7c‐5p in the inflammation and osteogenesis in dental pulp stem cells (DPSCs) was explored. The level of let‐7c‐5p in DPSCs was up‐regulated, and the cells were subjected to lipopolysaccharide (LPS) to induce inflammation. The effect of let‐7c‐5p on cell proliferation potential, osteogenic differentiation potential, and activity of HMGA2/PI3K/Akt pathway was detected. The administration of LPS suppressed the cell proliferation of DPSCs and suppressed calcium deposition, activity of alkaline phosphatase (ALP), and levels of OCN, OPN, OSX, MSX2, and RUNX2 in inflamed DPSCs. The impaired osteogenic differentiation of inflamed DPSCs was associated with the increased levels of HMGA2, p‐PI3K, and p‐Akt. In let‐7c‐5p‐overexpressed inflamed DPSCs, the proliferation and osteogenic differentiation potential of DPSCs were restored, and the activation of HMGA2/PI3K/Akt signalling was inhibited. In rat pulpitis models, the injection of let‐7c‐5p agomir restored the osteogenic differentiation potential of dental pulp cells and inhibited HMGA2/PI3K/Akt signalling. The findings demonstrated the anti‐inflammation and pro‐osteogenesis effect of let‐7c‐5p during the attack of pulpitis, which depended on the inhibition of HMGA2/PI3K/Akt signalling.
BackgroundLet-7c-5p is down-regulated in dental pulp tissues in inflammatory disorders. The microRNA (miR) molecule shows an anti-inflammation potential due to its direct regulation of dentin matrix protein-1 (DMP1), which promotes inflammation changes in dental pulp tissues. In the present study, the effect of let-7c-5p on lipopolysaccharide (LPS)-induced pulpitis was detected and the associated mechanism was explored.Material/MethodsDental pulp stem cells (DPSCs) were isolated from rat dental tissues, infected with let-7c-5p lentivirus particles, and subjected to LPS administration to induce inflammation. Then, the effect of let-7c-5p overexpression on LPS-induced impairments on DPSCs were detected and the mechanism was explained by focusing on the DMP1 expression and NF-κB pathway. The role of DMP1 in the anti-inflammation effect of let-7c-5p was assessed by incubating let-7c-5p-expressed DPSCs with DMP1 protein. The results of in vitro assays were verified in LPS-induced rat pulpitis models.ResultsLPS administration increased the production of IL-1β and TNF-α and decreased DPSCs viability by increasing the expression of DMP1 and activating NF-κB pathway. However, the induced expression of let-7c-5p relieved DPSCs from LPS-induced inflammation and suppressed DMP1 as well as NF-κB pathway. The incubation of let-7c-5p-expressed DPSCs with DMP1 protein blocked the effect of let-7c-5p. In in vivo experiments, the injection of let-7c-5p attenuated LPS-induced pulpitis by inhibiting DMP1-mediated NF-κB pathway.ConclusionsFindings outlined in the current study demonstrated the dental pulp protecting function of let-7c-5p during LPS-induced inflammation, which was exerted by inhibiting the DMP1-mediated NF-κB pathway.
Recently, additional long noncoding RNAs (lncRNAs) have been identified and their possible roles were investigated in a variety of human tumors. One of these lncRNAs, LINC01929, promoted the progression of some cancers, whereas its expression and biological function in human oral squamous cell carcinoma (OSCC) remains still mostly uncertain. The LINC01929 expression in OSCC tissues or cell lines was identified via quantitative real-time polymerase chain reaction. The cell counting kit-8, transwell migration, wound-healing, and flow cytometry assays were utilized to characterize the functions of LINC01929 in OSCC cells. The interactive relationships between LINC01929 and miR-137-3p, miR-137-3p and Forkhead box C1 (FOXC1) were investigated by the dual-luciferase activity assay. Our findings demonstrated that LINC01929 was highly expressed in OSCC tissue samples and cell lines, whereas miR-137-3p expression was downregulated. LINC01929 acted as a carcinogenic lncRNA with accelerated OSCC cell proliferation, migration and invasion, and suppression of apoptosis. We further indicated that LINC01929 facilitated tumor growth in xenograft mouse models. Mechanistically, LINC01929 acted as a sponge for miR-137-3p to elevate FOXC1 expression, which is the target of miR-137-3p. In addition, downregulated miR-137-3p expression rescued the suppressive behaviors of LINC01929 knockdown on the biological behaviors of OSCC cells. Taken together, LINC01929 functioned as a tumor-promoting lncRNA via the miR-137-3p/FOXC1 axis in OSCC, suggesting novel targets for OSCC therapy.
BackgroundA number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC). MethodsWe rst examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and ow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumour domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. ResultsOSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF2361 levels in patients with OSCC correlated with a poor prognosis.CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression. ConclusionCircZNF236 modulates OSCC via an miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.
BackgroundA number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC).MethodsWe first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumour domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. ResultsOSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF2361 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression.ConclusionCircZNF236 modulates OSCC via an miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.
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