scholarly journals MiR-137's Tumor Suppression on Prolactinomas by Targeting MITF and Modulating Wnt Signaling Pathway

2019 ◽  
Vol 104 (12) ◽  
pp. 6391-6402 ◽  
Author(s):  
Cao Lei ◽  
Guo Jing ◽  
Wang Jichao ◽  
Lou Xiaohui ◽  
Qiuyue Fang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Tumor Suppression ◽  
Inhibitory Factor ◽  
Luciferase Reporter ◽  
Wnt Inhibitory Factor 1 ◽  
Mitf Expression ◽  
Inhibitory Factor 1

Abstract Context Prolactinomas are the most common functional pituitary adenomas; the aggressive tumors still present challenge to clinicians. Aberrant expression of miRNAs has been functionally associated with prolactinomas. Objective Here we explored the role of miR-137 on the proliferation, invasion, and apoptosis of prolactinomas and its possible mechanism. Results Low expression of miR-137 was correlated with the invasive behavior of human prolactinomas and predicted high recurrence. MiR-137 inhibited cell proliferation, invasion, and survivals of MMQ and GH3 cells and reduced tumor volume in F344 rat prolactinomas. The luciferase reporter assay confirmed that microphthalmia-associated transcription factor (MITF) was the direct target of miR-137. In addition, miR-137 mimics could inhibit MITF expression in vivo and in vitro. Upregulation of MITF expression promoted cell proliferation, invasion, and survivals and reversed the antitumor effect of miR-137 in vivo and in vitro. Furthermore, miR-137 could also upregulate wnt-inhibitory factor-1 and inhibit nuclear translocation of β-catenin. Upregulation of wnt-inhibitory factor-1 with decitabine can enhance the inhibition on cell proliferation of miR-137. A glycogen synthase kinase-3 inhibitor, SB 216763, promoted cell proliferation by upregulation of total/cytoplasmic/nuclear β-catenin and reversed tumor suppression of miR-137 mimics. Conclusions Our data suggest that miR-137 possesses a tumor invasive suppressor function with a prognostic value in prolactinomas by targeting MITF and modulating Wnt-β-catenin signaling pathway.

scholarly journals miR-142-5p regulates the progression of diabetic retinopathy by targeting IGF1

2020 ◽  
Vol 34 ◽  
pp. 205873842090904 ◽  
Author(s):  
Xiuming Liu ◽  
Jianchang Li ◽  
Xiaofeng Li
Keyword(s):  
Cell Proliferation ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Igf1r Signaling

As one of leading causes of blindness, diabetic retinopathy (DR) is a progressive microvascular complication of diabetes mellitus (DM). Despite significant efforts have been devoted to investigate DR over the years, the molecular mechanisms still remained unclear. Emerging evidences demonstrated that microRNAs (miRNAs) were tightly associated with pathophysiological development of DR. Hence, this study was aimed to illustrate the role and molecular mechanisms of miR-412-5p in progression of DR. Streptozotocin (STZ) treatment in rats and human retinal endothelial cell (HREC) models were used to simulate DR conditions in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to demonstrate the morphology of retinal tissues of rats. Qualitative real-time polymerase chain reaction (qRT-PCR) detected miR-142-5p and vascular endothelial growth factor (VEGF) expression levels. Cell counting kit-8 (CCK8) assay and immunofluorescence (IF) measured the cell proliferation rates. Western blot tested the expression status of IGF1/IGF1R-mediated signaling pathway. Dual-luciferase reporter assays demonstrated the molecular mechanism of miR-142-5p. miR-142-5p level was down-regulated in retinal tissues of DR rats and high glucose (HG)-treated HRECs. Insulin-like growth factor 1 (IGF1) was identified as a direct target of miR-142-5p. The reduced miR-142-5p level enhanced HRECs proliferation via activating IGF/IGF1R-mediated signaling pathway including p-PI3K, p-ERK, p-AKT, and VEGF activation, ultimately giving rise to cell proliferation. Either miR-142-5p overexpression or IGF1 knockdown alleviated the pathological effects on retinal tissues in DR rats. Collectively, miR-142-5p participated in DR development by targeting IGF1/p-IGF1R signaling pathway and VEGF generation. This miR-142-5p/IGF1/VEGF axis provided a novel therapeutic target for DR clinical treatment.

scholarly journals Curcumin Inhibits Hepatocellular Carcinoma via Regulating miR-21/TIMP3 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Jingtao Li ◽  
Hailiang Wei ◽  
Yonggang Liu ◽  
Qian Li ◽  
Hui Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Anticancer Effects ◽  
Cell Proliferation Inhibition

Background/Aim. Curcumin exhibits anticancer effects against various types of cancer including hepatocellular carcinoma (HCC). miR-21 has been reported to be involved in the malignant biological properties of HCC. However, whether miR-21 plays a role in curcumin-mediated treatment of HCC is unknown. The purpose of this study was to identify the potential functions and mechanisms of miR-21 in curcumin-mediated treatment of HCC. Methods. The anticancer effects of curcumin were assessed in vivo and in vitro. The underlying mechanism of miR-21 in curcumin-mediated treatment of HCC was assessed by quantitative real-time PCR (RT-qPCR), western blot, and Dual-Luciferase Reporter assays. Results. The present study revealed that curcumin suppressed HCC growth in vivo and inhibited HCC cell proliferation and induced cell apoptosis in a dose-dependent manner in vitro. Meanwhile, the curcumin treatment can downregulate miR-21 expression, upregulate TIMP3 expression, and inhibit the TGF-β1/smad3 signaling pathway. miR-21 inhibition enhanced the effect of curcumin on cell proliferation inhibition, apoptosis, and TGF-β1/smad3 signaling pathway inhibition in HepG2 and HCCLM3 cells. It demonstrated that TIMP3 was a direct target gene of miR-21. Interestingly, the effect of miR-21 inhibition on cell proliferation, apoptosis, and TGF-β1/smad3 signaling pathway in HepG2 and HCCLM3 cells exposed to curcumin was attenuated by TIMP3 silencing. Conclusion. Taken together, the present study suggests that miR-21 is involved in the anticancer activities of curcumin through targeting TIMP3, and the mechanism possibly refers to the inhibition of TGF-β1/smad3 signaling pathway.

scholarly journals miR-20a-5p/RBM24 Axis Alleviated Hypertensive Intracerebral Hemorrhage via Regulating HIF1α/VEGFA Signaling Pathway

2021 ◽  
Author(s):  
Li Xu ◽  
Chuangqi Mo ◽  
Ming Lu ◽  
Pingping Wang ◽  
Yue Liu
Keyword(s):  
Cell Proliferation ◽  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Clinicopathological Characteristics ◽  
Tube Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Hypertensive Intracerebral Hemorrhage

Abstract Background: Hypertensive intracerebral hemorrhage presented high incidence and high mortality owing to its difficult to diagnose. However, the molecular mechanism of HICH remains unclear. Therefore, this study aims to investigate the key miRNAs and the mechanism of the key miRNAs in HICH. Methods: miRNAs chip was used to explore the differentially expressed miRNAs in HICH patients. In vitro and in vivo HICH models were established by Ang-II. Cell Counting Kit-8 (CCK8), flow cytometry, transwell assay and tube formation analysis were used to detect cell proliferation, apoptosis, cell migration and tube formation, respectively. Hematoxylin-eosin staining was used to evaluate the intracerebral hemorrhage in vivo HICH model. The regulatory mechanism of miR-20a-5p in HICH was confirmed by dual luciferase reporter assay, immunofluorescence, qRT-PCR, western blot and rescue experiments. Results: miR-20a-5p showed the most downregulated in HICH patients compared with healthy individuals and significantly associated with clinicopathological characteristics of HICH. Upregulation of miR-20a-5p promoted cell proliferation, migration and tube formation while inhibited apoptosis in vitro and ameliorated the development of HICH in vivo. RBM24 is a direct target of miR-20a-5p and silencing RBM24 could partially recovery the development of HICH caused by miR-20a-5p inhibition both in vivo and in vitro. miR-20a-5p regulated the development of HICH depending on HIF1α/VEGFA pathway. Conclusion: Our results demonstrated that miR-20a-5p/RBM24 axis regulated hypertensive intracerebral hemorrhage via regulating HIF1α/VEGFA signaling pathway, in support of further investigation into miR-20a-5p therapies for HICH treatment.

scholarly journals Inhibition of microRNA-299-5p sensitizes glioblastoma cells to temozolomide via the MAPK/ERK signaling pathway

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yujiang Peng ◽  
Xijun He ◽  
Huihui Chen ◽  
Hongyu Duan ◽  
Bo Shao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Chemotherapy Resistance ◽  
Erk Signaling ◽  
Luciferase Reporter ◽  
Control Group ◽  
Cell Cycle Distribution ◽  
Western Blots

Glioblastomas (GBMs) are a lethal class of brain cancer, with a median survival <15 months in spite of therapeutic advances. The poor prognosis of GBM is largely attributed to acquired chemotherapy resistance, and new strategies are urgently needed to target resistant glioma cells. Here we report a role for miR-299-5p in GBM. The level of miR-299-5p expression was detected in glioma specimens and cell lines by qRT-PCR. Luciferase reporter assays and Western blots were performed to verify GOLPH3 as a direct target of miR-299-5p. In vitro cell proliferation, invasion, cell cycle distribution, and apoptosis were assessed to determine whether or not miR-299-5p knockdown sensitized GBM cells to temozolomide (TMZ). We demonstrated that miR-299-5p levels were up-regulated in the GBM groups compared with the normal control group. The highest expression of miR-129-5p occurred in the highest GBM stage. miR-299-5p knockdown significantly inhibited the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway. We also showed that miR-299-5p knockdown enhanced sensitivity of GBM cells to TMZ both in vitro and in vivo by inhibiting cell proliferation and invasion and promoting apoptosis. In addition, we demonstrated that GOLPH3 is a novel functional target of miR-299-5p. GOLPH3 regulates the MAPK/ERK axis under miR-299-5p regulation. In conclusion, we identified a link between miR-299-5p expression and the GOLPH3/MAPK/ERK axis, thus illustrating a novel role for miR-299-5p in GBM.

scholarly journals Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 20 ◽  
pp. 153303382199007
Author(s):  
Wenlin Liu ◽  
Jiandong Zhan ◽  
Rong Zhong ◽  
Rui Li ◽  
Xiaoli Sheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Laryngeal Cancer ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Lncrna Gas5

Background: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. Methods: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. Results: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. Conclusion: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals Oncogene APOL1 promotes proliferation and inhibits apoptosis via activating NOTCH1 signaling pathway in pancreatic cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Jiewei Lin ◽  
Zhiwei Xu ◽  
Junjie Xie ◽  
Xiaxing Deng ◽  
Lingxi Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Density Lipoprotein ◽  
Human Pancreatic Cancer ◽  
Luciferase Reporter ◽  
Notch1 Signaling ◽  
In Vivo Experiments ◽  
Notch1 Signaling Pathway

AbstractAPOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.

scholarly journals Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jingpeng Wang ◽  
Shuyuan Li ◽  
Gaofeng Zhang ◽  
Huihua Han
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Volatile Anesthetic ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

scholarly journals METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaoping Zhang ◽  
Dan Li ◽  
Chengyou Jia ◽  
Haidong Cai ◽  
Zhongwei Lv ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Qrt Pcr ◽  
The Relationship

Abstract Background Papillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood. Methods Expression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC. Results Functional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways. Conclusions Collectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.

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