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Background: Identifying the factors affecting osteoblast differentiation of periodontal ligament cells (PDLCs) can help enhance the regeneration of periodontal tissue. LncRNA plasmacytoma variant translocation 1 (lncPVT1) is an important regulatory factor involved in many biological processes, but its role in osteogenesis remains unclear.Methods: Expressions of osteogenic markers were detected by quantitative reverse transcription polymerase chain reaction and Western blot analysis. Alkaline phosphatase staining was conducted for early osteoblast differentiation and alizarin red S staining was used for mineral deposition. RNA sequencing was used to identify the miRNAs regulated by lncPVT1 during osteogenesis. Cell transfection was used to overexpress or knockdown lncPVT1 and miR-10a-5p. Dual luciferase reporter assays were conducted to analyze the binding of miR-10a-5p to brain-derived neurotrophic factor (BDNF).Results: LncPVT1 was significantly increased during osteogenic induction of PDLCs. Overexpression of lncPVT1 promoted osteogenesis, whereas lncPVT1 knockdown inhibited this process. RNA sequencing showed that miR-10a-5p expression was significantly increased after lncPVT1 knockdown. RNA immunoprecipitation assay further demonstrated the binding potential of lncPVT1 and miR-10a-5p. MiR-10a-5p inhibited the osteogenesis of PDLCs, and partially reversed the stimulatory effects of lncPVT1. Subsequently, we identified a predicted binding site for miR-10a-5p on BDNF and confirmed it using dual luciferase reporter assays. Moreover, lncPVT1 upregulated the expression of BDNF, whereas miR-10a-5p downregulated BDNF expression. BDNF promoted osteogenesis and partially rescued the si-lncPVT1-mediated inhibition of PDLCs osteogenic differentiation.Conclusions: LncPVT1 positively regulated the osteogenic differentiation of PDLCs via miR-10a-5p and BDNF. Our results provide a promising target for enhancing the osteogenic potential of PDLCs. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a major cause of morbidity and mortality in patients with various cardiovascular diseases. Restoration of cardiac function is critical in improving the clinical outcomes of patients with HF. Long noncoding RNAs are widely involved in the development of multiple cardiac diseases, whereas their role in regulating cardiac function remains unclear. In this study, we found that the expression of long noncoding RNA-DACH1 (dachshund homolog 1) was upregulated in the failing hearts of mice and human. We tested the hypothesis that the intronic long noncoding RNA of DACH1 (LncDACH1) can participate in the regulation of cardiac function and HF. Transgenic overexpression of LncDACH1 in the cardiac myocytes of mice led to impaired cardiac function, reduced calcium transient and cell shortening, and decreased SERCA2a (sarcoplasmic reticulum calcium ATPase 2a) protein expression. In contrast, conditional knockout of LncDACH1 in cardiac myocytes resulted in increased calcium transient, cell shortening, SERCA2a protein expression, and improved cardiac function of transverse aortic constriction induced HF mice. The same qualitative data were obtained by overexpression or knockdown of LncDACH1 with adenovirus carrying LncDACH1 or its siRNA. Moreover, therapeutic administration of adenovirus carrying LncDACH1 siRNA to transverse aortic constriction mice abolished the development of HF. Mechanistically, LncDACH1 directly binds to SERCA2a. Overexpression of LncDACH1 augments the ubiquitination of SERCA2a. LncDACH1 upregulation impairs cardiac function by promoting ubiquitination-related degradation of SERCA2a. [ABSTRACT FROM AUTHOR]

Atherosclerosis is one of the most common vascular diseases, and inflammation participates in all stages of its progression. Laminar shear stress protects arteries from atherosclerosis and reduces endothelial inflammation. Long noncoding RNAs have emerged as critical regulators in many diseases, including atherosclerosis. However, the expression and functions of long noncoding RNAs subjected to laminar shear stress in endothelial cells remain unclear. This study aimed to reveal the mechanism by which shear stress-regulated long noncoding RNAs contribute to anti-inflammation. In this study, we identified a novel long noncoding RNA AF131217.1, which was upregulated after laminar shear stress treatment in human umbilical vein endothelial cells. Knockdown of AF131217.1 inhibited flow-mediated reduction of monocyte adhesion VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) expression and inhibited flow-mediated enhancement of flow-responsive expression of KLF (Kruppel-like factor) 2 and eNOS (endothelial NO synthase). Furthermore, TNF-α (tumor necrosis factor-α) was used to induce an inflammatory response in human umbilical vein endothelial cells. Knockdown of AF131217.1 promoted ICAM-1 and VCAM-1 expression, as well as changes in monocyte adhesion and KLF2 and eNOS expression induced by TNF-α. Mechanistic investigations indicated that AF131217.1 acted as a competing endogenous RNA for miR-128-3p, leading to regulation of its target gene KLF4. In conclusion, our study demonstrates for the first time that laminar shear stress regulates the expression of AF131217.1 in human umbilical vein endothelial cells, and the AF131217.1/miR-128-3p/KLF4 axis plays a vital role in atherosclerosis development. [ABSTRACT FROM AUTHOR]

Preeclampsia is a pregnancy-specific hypertensive disorder, which seriously undermines the health of maternity and fetus. However, its cause and pathogenesis remain elusive. Flawed decidualization is considered to be related to preeclampsia. Increasing evidence indicates that long noncoding RNAs are correlated with a variety of diseases, including preeclampsia. In this study, we verified the expression of long noncoding RNA HK2P1 (hexokinase 2 pseudogene 1) and its cognate gene HK2 (hexokinase 2), which were found by our previous RNA-sequencing analysis in the decidua of severe preeclampsia patients and matched control subjects. Besides that, we also investigated the function and the mechanism of HK2P1 and HK2 during decidualization. HK2 is the crucial enzyme involved in glycolysis. The HK2P1 and HK2 genes are homologous to each other. The results demonstrated that HK2P1, like HK2, stimulated the glucose uptake and lactate production of human endometrial stromal cells. In addition, HK2P1 and HK2 are indispensable for endometrial decidualization. Downregulated HK2P1 or HK2 inhibited human endometrial stromal cells proliferation and differentiation. Furthermore, there was a significant positive correlation between the expression of HK2P1 and HK2, and HK2P1 regulated the HK2 expression via competition for the shared miR-6887-3p. Taken together, our results indicated that the reduced expression of HK2P1 and HK2 may have contributed to the occurrence and development of preeclampsia by suppressing glycolysis and impairing decidualization. Our study would be helpful to understand the pathogenesis and the regulatory network of preeclampsia. [ABSTRACT FROM AUTHOR]

Purpose While lncRNAs (long noncoding RNAs) have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle invasive bladder cancer remain largely unknown. We identified a lncRNA termed lncRNA- UNMIBC (up-regulated in nonmuscle invasive bladder cancer) and evaluated its prognostic value in patients with primary nonmuscle invasive bladder cancer. Materials and Methods We analyzed the expression of lncRNA- UNMIBC in the tissues of 75 cases of primary nonmuscle invasive bladder cancer and adjacent normal mucosa by quantitative real-time polymerase chain reaction. Data were compared with clinicopathological parameters using the Kaplan-Meier method and multivariate Cox regression analysis. The functions of lncRNA- UNMIBC were assessed by silencing the lncRNA in vitro and in vivo. RNA immunoprecipitation was performed to assay whether lncRNA- UNMIBC could be physically associated with EZH2 (enhancer of zeste homolog 2) and SUZ12 (SUZ12 polycomb repressive complex 2 subunit), which are core components of PRC2 (polycomb repressive complex 2). Chromatin immunoprecipitation was done to examine histone modification status. Results The expression level of lncRNA- UNMIBC was up-regulated in the tissues of 45 cases of primary nonmuscle invasive bladder cancer compared with normal mucosa. Kaplan-Meier estimates showed that lncRNA- UNMIBC expression was significantly associated with recurrence (log rank test p = 0.0151). We also found that lncRNA- UNMIBC had a key role in G0/G1 arrest. Furthermore, RNA and chromatin immunoprecipitation assays demonstrated that lncRNA- UNMIBC was physically associated with EZH2 and SUZ12, leading to an altered histone H3 lysine 27 methylation status of target genes. Conclusions These findings indicate that lncRNA- UNMIBC can facilitate tumor growth and may act as a negative prognostic factor of recurrence. [ABSTRACT FROM AUTHOR]

Laryngeal carcinoma is the second common malignancy of the upper aerodigestive tract after lung cancer; in most cases is a squamous cell carcinoma, whose risk factors include tobacco smoking and alcohol consumption. Despite therapeutic progress, the five-year overall survival rate for this malignancy has remained nearly 50% and many patients already present metastasis at the time of diagnosis. To date, there are no tools that predict the evolution of laryngeal carcinoma: in this light, during the last years, many studies were planned with the aim to investigate the role played by different biomarkers expressed by larynx cancer, which can help make an early diagnosis, predict disease evolution and direct therapeutic choice. This review aims to summarize these markers and correlating them with disease evolution. • The 5-year overall survival rate of laryngeal carcinoma has remained nearly 50%. • To date, there are no tools that predict the evolution of laryngeal carcinoma. • Many biomarkers expressed by larynx cancer play a role in its evolution. • They can aid in earlier diagnosis, clinical outcome and therapeutic choice. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Long noncoding RNA (lncRNA) can regulate various physiological and pathological processes through multiple molecular mechanisms in cis and in trans. However, the role of lncRNAs in cardiac hypertrophy is yet to be fully elucidated. Methods: A mouse lncRNA microarray was used to identify differentially expressed lncRNAs in the mouse hearts following transverse aortic constriction–induced pressure overload comparing to the sham-operated samples. The direct impact of one lncRNA, Ahit , on cardiomyocyte hypertrophy was characterized in neonatal rat cardiomyocytes in response to phenylephrine by targeted knockdown and overexpression. The in vivo function of Ahit was analyzed in mouse hearts by using cardiac-specific adeno-associated virus, serotype 9–short hairpin RNA to knockdown Ahit in combination with transverse aortic constriction. Using catRAPID program, an interaction between Ahit and SUZ12 (suppressor of zeste 12 protein homolog) was predicted and validated by RNA immunoprecipitation and immunoblotting following RNA pull-down. Chromatin immunoprecipitation was performed to determine SUZ12 or H3K27me3 occupancy on the MEF2A (myocyte enhancer factor 2A) promoter. Finally, the expression of human Ahit (leukemia-associated noncoding IGF1R activator RNA 1 [LUNAR1]) in the serum samples from patients of hypertrophic cardiomyopathy was tested by quantitative real-time polymerase chain reaction. Results: A previously unannotated lncRNA, antihypertrophic interrelated transcript (Ahit), was identified to be upregulated in the mouse hearts after transverse aortic constriction. Inhibition of Ahit induced cardiac hypertrophy, both in vitro and in vivo, associated with increased expression of MEF2A, a critical transcriptional factor involved in cardiac hypertrophy. In contrast, overexpression of Ahit significantly attenuated stress-induced cardiac hypertrophy in vitro. Furthermore, Ahit was significantly upregulated in serum samples of patients diagnosed with hypertensive heart disease versus nonhypertrophic hearts (1.46±0.17 fold, P =0.0325). Mechanistically, Ahit directly bound and recruited SUZ12, a core PRC2 (polycomb repressive complex 2) protein, to the promoter of MEF2A, triggering its trimethylation on H3 lysine 27 (H3K27me3) residues and mediating the downregulation of MEF2A, thereby preventing cardiac hypertrophy. Conclusions: Ahit is a lncRNA with a significant role in cardiac hypertrophy regulation through epigenomic modulation. Ahit is a potential therapeutic target of cardiac hypertrophy. [ABSTRACT FROM AUTHOR]