Lnc-DC regulates cellular turnover and the HBV-induced immune response by TLR9/STAT3 signaling in dendritic cells

Zhao

2020

CMAR

This paper was aimed at investigating the regulatory mechanism of long noncoding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) in epithelial ovarian cancer (EOC). Materials and Methods: MALAT1 and miR-145-5p expression in the tissues, serum, and EOC cell lines (TOV-112D, TOV-21G) of patients with EOC were detected. The two genes were transfected into the cells via upregulating or downregulating their expression. Levels of apoptosis-related proteins (Caspase-3, Bax, Bcl-2) were analyzed. Mechanisms of cell proliferation, invasion, and apoptosis were studied. Results: MALAT1 was high expressed in EOC tissues, while miR-145-5p was poorly expressed in them. The areas under the curves (AUCs) of the two genes for diagnosing EOC were greater than 0.850, and the two had a significantly negative correlation. According to multivariate Cox regression analysis, high MALAT1 expression, tumor size, degree of differentiation, case staging, and lymph node metastasis were the independent risk factors affecting prognosis. The 5-year overall survival rate (OSR) of patients with low MALAT1 expression was remarkably higher than that of those with high expression. Overexpressing miR-145-5p and silencing MALAT1 could inhibit EOC cells from proliferating and invading, increase their apoptotic rate, and improve levels of the apoptosis-related proteins. After cotransfection with MALAT1-inhibitor + miR-145-5p-inhibitor, the proliferation and invasion of TOV-112D and TOV-21G cells were inhibited and the apoptotic rate rose more obviously. Inhibiting MALAT1 could increase miR-145-5p expression, thus inhibiting EOC cells from proliferating and invading and thereby increasing their apoptotic rate. Conclusion: MALAT1 promotes EOC cells' survival by downregulating miR-145-5p so it may become a new direction for EOC diagnosis and gene therapy.

Section: Discussionmentioning

confidence: 99%

<p>LncRNA MALAT1 Promotes Survival of Epithelial Ovarian Cancer Cells by Downregulating miR-145-5p</p>

Zhao

2020

CMAR

“…In addition to enhancing STAT3 activation, WFDC21P possibly participates in the regulation of STAT3 signaling. [54,55] As a regulator of WFDC21P, miR-4293 could further elevate STAT3 phosphorylation. Moreover, by regulating STAT3 activation, WFDC21P could elevate the expression of miR-4293.…”

Section: Discussionmentioning

confidence: 99%

miR-4293 Upregulates lncRNA WFDC21P by Directly Suppressing mRNA-Decapping Enzyme 2 to Promote Lung Carcinoma Proliferation

Zhang

Yan

et al. 2020

Preprint

Background: Emerging evidence shows that lncRNA WFDC21P could promote STAT3 phosphorylation and microRNA 4293 SNP is associated with the risk of carcinomas, but the oncogenic functions of WFDC21P and miR-4293 in lung carcinoma are unclear.Methods: mRNA sequencing of lung carcinoma and control para-carcinoma tissues was performed to screen the potential targets. WFDC21P and miR-4293 levels were evaluated in lung carcinoma cells and tissues by qRT-PCR. The function of WFDC21P and miR-4293 on proliferation, apoptosis and metastasis were assessed by MTT, FACS, western blot, transwell assays, colony formation assays and xenografts experiment. RNA immunoprecipitation assays were implemented to verify the relationship between WFDC21P and mRNA-decapping enzyme 2 (DCP2). Furthermore, gain/loss of miR-4293 functions were used to determine its targeting relationship of DCP2. Results: WFDC21P expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, WFDC21P promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified DCP2 can directly bind to WFDC21P and down-regulates its expression. DCP2 as a direct target of miR-4293 and its expression is suppressed by miR-4293. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With positive correlation to WFDC21P expression, miR-4293 also plays oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both WFDC21P and miR-4293. Conclusion: Our results establish oncogenic roles for both WFDC21P and miR-4293, and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in lung carcinoma pathogenesis.

Reviews in Medical Virology

“…The sustained activation of STAT3 induced by the phosphorylation of tyrosine residue 705 promotes the expression of genes involved in dendritic cell differentiation . lncRNA ‐DC is also implicated in the immune response to HBV and acts by reducing the concentration of secreted TNF‐α, IL‐6, IL‐12, and IFN‐γ, as well as increasing the IL‐1β concentration in dendritic cells …”

Section: Regulation Of Viral Replication By Lncrna‐mediated Innate Immentioning

confidence: 99%

Long noncoding RNAs: Novel regulators of virus‐host interactions

Liu

et al. 2019

Long noncoding RNAs (lncRNAs) represent a key class of cellular regulators, involved in the modulation and control of multiple biological processes. Distinct classes of lncRNAs are now known to be induced by host cytokines following viral infections.Current evidence demonstrates that lncRNAs play essential roles at the hostpathogen interface regulating viral infections by either innate immune responses at various levels including activation of pathogen recognition receptors or by epigenetic, transcriptional, and posttranscriptional effects. We review the newly described mechanisms underlying the interactions between lncRNAs, cytokines, and metabolites differentially expressed following viral infections; we highlight the regulatory networks of host antiviral responses and emphasize the need for interdisciplinary research between lncRNA biology and immunology to deepen understanding of viral pathogenesis.