scholarly journals MicroRNA-17-3p is upregulated in psoriasis and regulates keratinocyte hyperproliferation and pro-inflammatory cytokine secretion by targeting CTR9

2022 ◽  
Vol 66 (1) ◽  
Author(s):  
Qingwen Li ◽  
Jiao Zhang ◽  
Shougang Liu ◽  
Fangfei Zhang ◽  
Jiayi Zhuang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Cytokine ◽  
Target Gene ◽  
Skin Lesions ◽  
Cytokine Secretion ◽  
Luciferase Reporter ◽  
Psoriatic Skin ◽  
Immune Functions ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Psoriasis is a chronic inflammatory skin disease. Although miRNAs are reported to be associated with the pathogenesis of psoriasis, the contribution of individual microRNAs toward psoriasis remains unclear. The miR-17-92 cluster regulates cell growth and immune functions that are associated with psoriasis. miR-17-3p is a member of miR-17-92 cluster; however, its role in dermatological diseases remains unclear. Our study aims at investigating the effects of miR-17-3p and its potential target gene on keratinocytes proliferation and secretion of pro-inflammatory cytokine and their involvement in psoriasis. Initially, we found that miR-17-3p was upregulated in psoriatic skin lesions, and bioinformatic analyses suggested that CTR9 is likely to be a target gene of miR-17-3p. Quantitative reverse-transcriptase PCR and immunohistochemical analysis revealed that CTR9 expression was downregulated in psoriatic lesions. Using dual-luciferase reporter assays, we identified CTR9 as a direct target of miR-17-3p. Further functional experiments demonstrated that miR-17-3p promoted the proliferation and pro-inflammatory cytokine secretion of keratinocytes, whereas CTR9 exerted the opposite effects. Gain-of-function studies confirmed that CTR9 suppression partially accounted for the effects of miR-17-3p in keratinocytes. Furthermore, Western blot revealed that miR-17-3p activates the downstream STAT3 signaling pathway while CTR9 inactivates the STAT3 signaling pathway. Together, these findings indicate that miR-17-3p regulates keratinocyte proliferation and pro-inflammatory cytokine secretion partially by targeting the CTR9, which inactivates the downstream STAT3 protein, implying that miR-17-3p might be a novel therapeutic target for psoriasis.

scholarly journals Overexpression of NPTX2 Promotes Malignant Phenotypeof Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia

2020 ◽  
Author(s):  
Xiaotian Han ◽  
Yechen Lu ◽  
Xiaoqi Li ◽  
Lingfang Xia ◽  
Hao Wen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Poor Prognosis ◽  
Hypoxia Inducible Factor ◽  
Luciferase Reporter ◽  
Malignant Phenotype ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Neuronal Pentraxin

Abstract Background: Epithelial ovarian cancer(EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2)is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC.Methods: Bioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.Results: EOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment.Conclusions: The above results suggest that NPTX2 may play a novel role in ovarian cancer's malignant phenotype and act asa promising treatment target for EOC moleculartherapy.

scholarly journals Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaotian Han ◽  
Yechen Lu ◽  
Xiaoqi Li ◽  
Lingfang Xia ◽  
Hao Wen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Poor Prognosis ◽  
Molecular Therapy ◽  
Luciferase Reporter ◽  
Malignant Phenotype ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Neuronal Pentraxin

BackgroundEpithelial ovarian cancer (EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2) is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC.MethodsBioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.ResultsEOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment. NPTX2 knockdown abolished the hypoxia-induced malignant phenotypes in ECO.ConclusionsThe above results suggest that NPTX2 may play a novel role in ovarian cancer’s malignant phenotype and act as a promising treatment target for EOC molecular therapy.

scholarly journals LINC00893 Inhibits The Progression of Prostate Cancer Through miR-3173-5p/SOCS3/JAK2/STAT3 Pathway

2021 ◽  
Author(s):  
Chuigong Yu ◽  
Yu Fan ◽  
Yu Zhang ◽  
Lupeng Liu ◽  
Gang Guo
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Janus Kinase ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Stat3 Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Abstract Background: Prostate cancer (PCa) is one of the most common malignant tumors in the male urinary system. In recent years, the morbidity and mortality of PCa have been increasing due to the limited effects of existing treatment strategies. Long non-coding RNA (lncRNA) LINC00893 inhibits the proliferation and metastasis of papillary thyroid cancer (PTC) cells, but its role in PCa has not been reported. Our study aims to clarify the role and underlying mechanism of LINC00893 in regulating the progression of PCa.Methods: We analyzed LINC00893 expression through TCGA database. We also collected 66 paires of PCa tissues and matched para-cancerous tissues as well as cell lines and assessed LINC00893 expression. Subsequently, we conducted gain-of-function assays to confirm the role of LINC00893 in PCa. CCK-8, EdU, colony information and transwell assays were implemented to detect cell proliferation, colony formation and metastasis abilities, respectively. RT-qPCR and western blot assays were used to quantify the expression of mRNA and protein. Dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP) and RNA pull down assays were conducted to evaluate the interaction of molecules. Spearman correlation coefficient analysis was conducted to detect the correlation between molecules.Results: We found that the LINC00893 expression in PCa tissues and cell lines was upregulated compared with matched controls, and patients with low expression of LINC00893 suffered a low overall survival rate. Overexpression of LINC00893 hindered the proliferation, epithelial-mesenchymal transition (EMT) as well as metastasis of PCa cells in vitro and in vivo. In terms of mechanism, suppressor of cytokine signaling 3 (SOCS3)/Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway occupied a central position in the regulation of PCa progression by LINC00893. LINC00893 weakened the inhibition role of miR-3173-5p on SOCS3 expression through functioning as a miR-3173-5p sponge, which inhibited the JAK2/STAT3 signaling pathway. Conclusions: LINC00893 suppresses the progression of prostate cancer through miR-3173-5p/SOCS3/JAK2/STAT3 pathway. our data uncovers a novel mechanism by which LINC00893 hinders the progression of PCa, which enriches the molecular network of LINC00893 regulating the PCa progression and laies a theoretical foundation for PCa targeted therapy.

scholarly journals MicroRNA-214 prevents pulmonary angiogenesis and alveolarization in neonatal rats with hyperoxia-mediated impairment of lung development by blocking PlGF-dependent STAT3 signaling pathway

2020 ◽  
Author(s):  
Zhi-Qun Zhang ◽  
Xiao-Xia Li ◽  
Jing Li ◽  
Hui Hong ◽  
Xian-Mei Huang
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Preterm Infants ◽  
Neonatal Rat ◽  
Luciferase Reporter ◽  
Neonatal Rats ◽  
Stat3 Signaling ◽  
Pulmonary Epithelial Cells ◽  
Stat3 Signaling Pathway ◽  
Gene Assay

AbstractIn recent years, the roles of microRNAs (miRNAs) in pulmonary diseases have been widely studied and researched. However, the molecular mechanism by which miR-214 affects bronchopulmonary dysplasia (BPD) remains elusive and merits further exploration. Hence, this study aims to clarify the function of miR-214 in pulmonary angiogenesis and alveolarization in preterm infants with BPD. BPD neonatal rat model was induced by hyperoxia, and pulmonary epithelial cells were isolated from rats and exposed to hyperoxia. Gain- or loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were detected using RT-qPCR and western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene assay and RIP assay. ELISA was adopted to assess IL-1β, TNF-a, IL-6, ICAM-1 and Flt-1 expression in rats. Decreased miR-214 expression and elevated PlGF expression were evident in the lung tissues of neonatal rats with BPD. PlGF was a target of miR-214, and miR-214 downregulated PlGF to inactivate the STAT3 signaling pathway. miR-214 overexpression or PlGF silencing decreased apoptosis of hyperoxic pulmonary epithelial cells and declined pulmonary angiogenesis and alveolarization in BPD neonatal rats. Collectively, miR-214 can protects against pulmonary angiogenesis and alveolarization in preterm infants with BPD by suppressing PlGF and blocking STAT3 signaling pathway.

scholarly journals MiR-135-5p alleviates bone cancer pain by regulating astrocyte-mediated neuroinflammation in spinal cord through JAK2/STAT3 signaling pathway

2021 ◽  
Author(s):  
Ming Liu ◽  
Xuefeng Cheng ◽  
Hong Yan ◽  
Jingli Chen ◽  
Caihua Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cancer Pain ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Bone Cancer ◽  
Bone Cancer Pain ◽  
Luciferase Reporter ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Gene Assay

Bone cancer pain (BCP) was associated with microRNA dysregulation. In this study, we intended to clarify the potential role of miR-135-5p in a BCP mouse model, which was established by tumor cell implantation (TCI) in the medullary cavity of the mouse femur. The BCP related behaviors were tested, including the paw withdrawal mechanical threshold (PWMT) and number of spontaneous flinches (NSF). The miRNA expression profiles in astrocytes of the sham and tumor groups were compared, and miRNA microarray and quantitative real-time PCR (qRT-PCR) assays confirmed that the amount of expression of miR-135-5p was significantly decreased in astrocytes of the tumor group. Gain- and loss-of-function studies showed that miR-135-5p could inhibit astrocytes activation and inflammation cytokines (TNF-α and IL-1β) expression. The relation between miR-135-5p and JAK2 was detected by bioinformatic analysis and dual luciferase reporter gene assay. By conducting in vitro experiments, it was shown that the miR-135-5P mimics lowered the level of JAK2/STAT3 proteins and inflammatory factors in astrocytes. Moreover, in vivo analysis on BCP mice model indicated that the miR-135-5p agonist could sufficiently increase PWMT and decrease NSF. Meanwhile, reduced activation of astrocytes in the spinal cord, as well as decreased expression of JAK2/STAT3 and inflammatory mediators, were found after miR-135-5p agonist treatment. Collectively, the results showed that miR-135-5p could potentially reduce BCP in mice through inhibiting astrocyte-mediated neuroinflammation and blocking of the JAK2/STAT3 signaling pathway, indicating that the upregulation of miR-135-5P could be a therapeutic focus in BCP treatment.

scholarly journals Dihydroartemisinin inhibits IL-6-induced epithelial–mesenchymal transition in laryngeal squamous cell carcinoma via the miR-130b-3p/STAT3/β-catenin signaling pathway

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110094
Author(s):  
Yajing Sun ◽  
Xiuying Lu ◽  
Hui Li ◽  
Xiaoming Li
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Objective To explore whether dihydroartemisinin (DHA) can block interleukin (IL)-6-induced epithelial–mesenchymal transition (EMT) in laryngeal squamous cell carcinoma (LSCC). Methods The expression of SLUG, signal transducer and activator of transcription 3 (STAT3), and microRNA (miR)-130b-3p was measured. In addition, a dual-luciferase reporter assay was performed to examine the interaction of miR-130b-3p with STAT3. Results We found that IL-6 can promote EMT and invasion in LSCC cells, whereas DHA can inhibit these two processes. However, DHA alone does not influence EMT and cancer invasion. Furthermore, DHA upregulated miR-130b-3p, which can downregulate STAT3 and β-catenin protein expression and decrease the activity of the IL-6/STAT3 signaling pathway. Moreover, we found that miR-130b-3p can target STAT3 directly. Conclusions DHA can block IL-6-triggered EMT and invasion in LSCC, and during these processes, DHA increases miR-130b-3p expression to decrease the activation of the IL-6/STAT3 and β-catenin signaling pathways. These findings may provide new insights into strategies for suppressing and even preventing LSCC metastasis.

scholarly journals miRNA-331-3p Affects The Proliferation, Metastasis And Invasion of Osteosarcoma Through SOCS1/JAK2/STAT3

2021 ◽  
Author(s):  
Dan Zu ◽  
Qi Dong ◽  
Sunfang Chen ◽  
Yongde Chen ◽  
Jun Yao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Small Noncoding Rnas ◽  
Protein Levels ◽  
Stat3 Signaling ◽  
Survival Difference ◽  
Stat3 Signaling Pathway

Abstract Background: MicroRNAs (miRNA) are regulatory small noncoding RNAs, which play a key role in many cancers. It has been found that miR-331-3p is involved in the development and progression of various cancers, but there are few reports in osteosarcoma. Methods: The public GEO database was used to analyze the survival difference of miR-331-3p in OS organizations. The level of cell proliferation assay was assessed by CCK-8 and colony formation. Tanswell and Wound-healing detect the transfer and invasion ability of miR-331-3p in OS. TargetScan, miRDBmiR, TarBase, and dual luciferase reporter gene assays were used to determine SOCS1 as a targeted regulator. Western blot and immunohistochemistry were used to detect the expression of protein levels. A mouse model of subcutaneously transplantable tumors is used to evaluate the proliferation of OS in vivo.Results: The low expression of miR-331-3p is negatively correlated with the overall survival of OS patients. Overexpression of miR-331-3p significantly inhibited cell proliferation, metastasis and invasion. miR-331-3p affects the occurrence and development of osteosarcoma by targeting the SOCS1/JAK2/STAT3 signaling pathway.Conclusion: miR-331-3p reduces the expression of SOCS1 by combining with its 3'UTR, thereby activating the JAK2/STAT3 signaling pathway to regulate the progression of OS.

scholarly journals MicroRNA-214 Prevents Pulmonary Angiogenesis and Alveolarization in Rat Models with Bronchopulmonary Dysplasia via PlGF-Dependent STAT3 Signaling Pathway

2020 ◽  
Author(s):  
Zhi-Qun Zhang ◽  
Hui Hong ◽  
Jing Li ◽  
Xiao-Xia Li ◽  
Xian-Mei Huang
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Neonatal Rat ◽  
Luciferase Reporter ◽  
Neonatal Rats ◽  
Stat3 Signaling ◽  
Pulmonary Epithelial Cells ◽  
Stat3 Signaling Pathway

Abstract Background: In recent years, the roles of microRNAs (miRNAs) in pulmonary diseases have been widely studied and researched. However, the molecular mechanism by which miR-214 affects bronchopulmonary dysplasia (BPD) remains elusive and merits further exploration. Hence, this study aims to clarify the function of miR-214 in pulmonary angiogenesis and alveolarization in preterm infants with BPD. Methods: BPD neonatal rat model was induced by hyperoxia, and pulmonary epithelial cells were isolated from rats and exposed to hyperoxia. Gain- or loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were detected using RT-qPCR and western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene assay and RIP assay. ELISA was adopted to assess IL-1β, TNF-a, IL-6, ICAM-1 and Flt-1 expression in rats. Results: Decreased miR-214 expression and elevated PlGF expression were evident in the lung tissues of neonatal rats with BPD. PlGF was a target of miR-214, and miR-214 downregulated PlGF to inactivate the STAT3 signaling pathway. miR-214 overexpression or PlGF silencing decreased apoptosis of hyperoxic pulmonary epithelial cells and declined pulmonary angiogenesis and alveolarization in BPD neonatal rats. Conclusions: Collectively, miR-214 can protects against pulmonary angiogenesis and alveolarization in preterm infants with BPD by suppressing PlGF and blocking STAT3 signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document