Hsa_circ_0081069 facilitates tongue squamous cell carcinoma progression by modulating MAP2K4 expression via miR-634.

It has been demonstrated that circular RNA (circRNA) is involved in the progression of tongue squamous cell carcinoma (TSCC). The aim of this study was to investigate the intrinsic mechanism of circ_0081069 in TSCC progression. The expression levels of circ_00081069, miR-634, and mitogen-activated protein kinase kinase 4 (MAP2K4) in TSCC tissues and cells were detected by quantitative real-time PCR (qRT-PCR). Cell counting kit 8 assay, Edu assay, and flow cytometry assay were used to detect cell proliferation and cell cycle distribution. Transwell assay was used to detect cell migration and invasion abilities. Western blot analysis was performed to detect the protein expression. Dual-luciferase reporter assay was used to detect the targeting relationships of circ_0081069, miR-634 and MAP2K4. Immunohistochemical staining was used to measure MAP2K4-positive cells in tissues. The effect of circ_0081069 silencing on tumor formation in TSCC in vivo was explored by xenograft tumor assay. Circ_0081069 was highly expressed in TSCC tissues and cells. Silencing of circ_0081069 inhibited cell proliferation, cell cycle progress, cell migration and invasion in vitro, as well as hindered tumor growth in vivo. Mechanistically, circ_0081069 targeted miR-634 to negatively regulate miR-634 expression, and inhibition of miR-634 was able to weaken the inhibitory effect of circ_0081069 knockdown on proliferation, migration, and invasion of TSCC cells. MiR-634 targeted MAP2K4 and negatively regulated MAP2K4 expression, and overexpression of miR-634 inhibited TSCC cell proliferation, migration, and invasion, while co-overexpression of MAP2K4 was able to reverse the effects of miR-634 in TSCC cells. Circ_0081069 is involved in the regulation of proliferation, cycle progress, migration, and invasion of TSCC cells through the miR-634/MAP2K4 axis and has the potential to serve as a diagnostic biomarker and therapeutic target.

Hypoxia-inducible Factor 1α Contributes to Matrix Metalloproteinases 2/9 and Inflammatory Responses in Periodontitis.

Periodontitis is a prevalent condition characterized by inflammation and tissue destruction within the periodontium, with hypoxia emerging as a contributing factor to its pathogenesis. Hypoxia-inducible factor 1α (HIF-1α) has a crucial role in orchestrating adaptive responses to hypoxic microenvironments and has been implicated in various inflammatory-related diseases. Understanding the interplay between HIF-1α, matrix metalloproteinases (MMPs), and inflammatory responses in periodontitis could provide insights into its molecular mechanisms. We investigated the relationship between HIF-1α, MMP2, and MMP9 in gingival crevicular fluid (GCF) and periodontal ligament stem cells (PDLSCs) from periodontitis patients. The expression levels of HIF-1α, MMP2, MMP9, and inflammatory factors (IL-6, IL-1ß, TNF-α) were assessed using enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR). Additionally, osteogenic differentiation of PDLSCs was identified by alkaline phosphatase activity. Significantly elevated levels of HIF-1α, MMP2, and MMP9 were observed in GCF of periodontitis patients compared to controls. Positive correlations were found between HIF-1α and MMP2/MMP9, as well as with IL-6, IL-1ß, and TNF-α. Modulation of HIF-1α expression in PDLSCs revealed its involvement in MMP2/9 secretion and inflammatory responses, with inhibition of HIF-1α mitigating these effects. Furthermore, HIF-1α inhibition alleviated the reduction in osteogenic differentiation induced by inflammatory stimuli. Our findings elucidate the regulatory role of HIF-1α in MMP expression, inflammatory responses, and osteogenic differentiation in periodontitis. In conclusion, targeting HIF-1α signaling pathways may offer therapeutic opportunities for managing periodontitis and promoting periodontal tissue regeneration.

Downregulation of circLPAR3 inhibits tumor progression and glycolysis by liberating miR-144-3p and upregulating LPCAT1 in oral squamous cell carcinoma.

Background: Increasing evidence demonstrated the important roles of circular RNAs (circRNAs) in human cancer progression, including oral squamous cell carcinoma (OSCC). The study intentions were to explore the role and molecular mechanism of hsa_circ_0004390 (circLPAR3) in OSCC progression. Methods: Expression of circLPAR3 in collected samples and cultured cell lines was detected with real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Loss-of-function experiments were performed to determine the effect of circLPAR3 silencing on OSCC cell proliferation, migration, invasion, apoptosis, angiopoiesis, and glycolysis. The sponge function of circLPAR3 was predicted by bioinformatics analysis and validated by the dual-luciferase reporter and RNA pull-down assays. In vivo experiments were conducted to validate the function of circLPAR3. Results: A marked increase in circLPAR3 expression was observed in OSCC samples and cell lines. Furthermore, circLPAR3 could distinguish OSCC samples from paired non-tumor samples, and patients with high circLPAR3 expression had a poor prognosis. Furthermore, circLPAR3 inhibition decreased OSCC growth in xenograft mouse models. Moreover, circLPAR3 silencing repressed cell proliferation, migration, invasion, angiopoiesis, glycolysis, and induced cell apoptosis in OSCC cells in vitro. Mechanically, circLPAR3 sponged miR-144-3p to prohibit the inhibiting effect of miR-144-3p on LPCAT1, thus promoting OSCC progression. Conclusion: CircLPAR3 exerted a tumor-promoting effect on OSCC growth through elevating LPCAT1 expression via functioning as a miR-144-3p sponge. This study supports the possible role of circLPAR3 in the diagnosis, prognosis, and treatment of OSCC.

The histone acetyltransferase p300 regulates the expression of pluripotency factors and odontogenic differentiation of human dental pulp cells.

p300 is a well-known histone acetyltransferase (HAT) and coactivator that plays vital roles in many physiological processes. Despite extensive research on the involvement of p300 in the regulation of transcription in numerous cell lines, the roles of this protein in regulating pluripotency genes and odontogenic differentiation in human dental pulp cells (HDPCs) are poorly understood. To address this issue, we investigated the expression of OCT4, NANOG and SOX2 and the proliferation and odontogenic differentiation capacity of HDPCs following p300 overexpression. We found that p300 overexpression did not overtly affect the ability of HDPCs to proliferate. The overexpression of p300 upregulated the promoter activity and the mRNA and protein expression of NANOG and SOX2. The HAT activity of p300 appeared to partially mediate the regulation of these factors; indeed, when a mutant form of p300 lacking the HAT domain was overexpressed, the promoter activity and expression of NANOG and SOX2 decreased relative to p300 overexpression but was greater than in the control. Furthermore, we demonstrated that the mRNA levels of the odontogenic marker genes dentine matrix protein-1 (DMP-1), dentin sialophosphoprotein (DSPP), dentin sialoprotein (DSP), osteopontin (OPN) and osteocalcin (OCN) were significantly decreased in HDPCs overexpressing p300 cultured under normal culture conditions and increased in HDPCs inducted to undergo odontogenic differentiation. This finding was further confirmed by measuring levels of alkaline phosphatase (ALP) activity and assessing the formation of mineralized nodules. The HAT activity of p300 had no significant effect on odontogenic differentiation. p300 was recruited to the promoter regions of OCN and DSPP and might be acting as a coactivator to increase the acetylation of lysine 9 of histone H3 of OCN and DSPP. Collectively, our results show that p300 plays an important role in regulating the expression of key pluripotency genes in HDPCs and modifying odontogenic differentiation.