Effect of SRY-Related High Mobility Group Box 9 on Extracellular Signal-Regulated Kinase/p38 Signaling Pathway in Glioma

2021 ◽  
Vol 11 (1) ◽  
pp. 171-175
Author(s):  
Tianlong Quan ◽  
Chunhua Zhang ◽  
Xin Song ◽  
Lu Wang
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
High Mobility ◽  
Negative Control ◽  
Glioma Cell Line ◽  
High Mobility Group ◽  
Control Group

As a common malignant tumor in neurosurgery, glioma is characterized as high incidence rate, easy to invade, metastasize and recurrent. It is difficult to treat and has a poor prognosis. The gliomas pathogenesis is complex and has not been fully resolved. Therefore, finding effective molecular targets for glioma is beneficial to improve therapeutic effect. The SRY-related high mobility group box 9 (SOX9) gene involves in mammalian development and is significantly increased in glioma. However, SOX9’s role in gliomas is unclear. The glioma cell line U87 was assigned into control group, scramble group that was transfected with siRNA negative control, and SOX9 siRNA group that was transfected with SOX9 siRNA followed by analysis of SOX9 mRNA and protein level by qPCR and Western blot, cell proliferation by MTT assay, cell apoptosis by Caspase 3 activity assay, cell invasion by Transwell assay, and MMP-9 level by ELISA. SOX9 siRNA transfection significantly downregulated SOX9 mRNA and protein expressions, inhibited U87 cell proliferation, enhanced Caspase 3 activity, suppressed cell invasion of U87, decreased the secretion of MMP-9 in the supernatant, and reduced ERK1/2 and P38 phosphorylation levels (P < 0.05). SOX9 can regulate the progression of glioma by regulating ERK/P38 signaling pathway, promoting cell apoptosis, inhibiting cell proliferation, and restraining cell invasion.

Effects of Papaya Leaf Extract (Carica papaya L.) on Cellular Proliferation and Apoptosis in Cervical Cancer Mice Model

2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Hela Cells ◽  
Leaf Extract ◽  
Caspase 3 ◽  
Methanol Extract ◽  
Negative Control ◽  
Proliferation Index ◽  
Control Group ◽  
P53 Expression

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.

scholarly journals Neochamaejasmin A Induces Mitochondrial-Mediated Apoptosis in Human Hepatoma Cells via ROS-Dependent Activation of the ERK1/2/JNK Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yangfang Ding ◽  
Qi Xie ◽  
Wenjing Liu ◽  
Zhaohai Pan ◽  
Xinmei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Morphological Changes ◽  
Control Group ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

The botanical constituents of Stellera chamaejasme Linn. exhibit various pharmacological and medicinal activities. Neochamaejasmin A (NCA), one main active constituent of S. chamaejasme, inhibits cell proliferation and induces cell apoptosis in several types of tumor cells. However, the antitumor effect of NCA on hepatocellular carcinoma cells is still unclear. In this study, NCA (36.9, 73.7, and 147.5 μM) significantly inhibited hepatoblastoma-derived HepG2 cell proliferation in a concentration-dependent manner. Hoechst 33258 staining and flow cytometry showed that apoptotic morphological changes were observed and the apoptotic rate was significantly increased in NCA-treated HepG2 cells, respectively. Additionally, the levels of Bax, cleaved caspase-3, and cytoplasmic cytochrome c were increased, while the level of Bcl-2 was decreased in NCA-treated HepG2 cells when compared with the control group. Moreover, we found that the reactive oxygen species (ROS) level was significantly higher and the mitochondrial membrane potential was remarkably lower in NCA-treated HepG2 cells than in the control group. Further studies demonstrated that the levels of p-JNK and p-ERK1/2 were significantly upregulated in NCA-treated HepG2 cells, and pretreatment with JNK and ERK1/2 inhibitors, SP600125 and PD0325901, respectively, suppressed NCA-induced cell apoptosis of HepG2 cells. In addition, NCA also significantly inhibited human hepatoma BEL-7402 cell proliferation and induced cell apoptosis through the ROS-mediated mitochondrial apoptotic pathway. These results implied that NCA induced mitochondrial-mediated cell apoptosis via ROS-dependent activation of the ERK1/2/JNK signaling pathway in HepG2 cells.

Effect of Silent Information Regulator on the Survival and Osteogenic Differentiation of Inflammatory Bone Marrow Mesenchymal Stem Cells by Regulating NF-κB Signaling Pathway

2020 ◽  
Vol 10 (1) ◽  
pp. 121-126
Author(s):  
Wenkun Lu ◽  
Tao Wang ◽  
Xunjian Gao ◽  
Fuqiang Yang ◽  
Jianjian Ge
Keyword(s):  
Cell Proliferation ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Adipogenic Differentiation ◽  
Control Group ◽  
Promote Cell Proliferation ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells ◽  
Inflammation Group

Osteogenic differentiation of BMSCs is beneficial for osteoarthritis (OA) treatment. Silent information regulator (SIRT1) plays a role in endocrine diseases and aging-related diseases. However, the role of SIRT1 in OA has not yet been elucidated. Rat BMSCs were isolated and divided into control group, inflammation group (BMSCs were cultured with IL-6), SIRT1 group (SIRT1 agonist Resveratrol was added under the action of IL-6) followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, ALP activity, expression of osteogenic genes Runx2 and OC and adipogenic differentiation gene PPARγ2 by Real time PCR, NF-κB expression by western blot and secretion of TNF-α and IL-6 by ELISA. In inflammation group, SIRT1 expression was significantly decreased, cell proliferation was significantly inhibited, and Caspase 3 activity was increased. Meanwhile, ALP activity, Runx2 and OC expression was decreased, PPARγ2 and NF-κB expression was increased, along with elevated TNF-α and IL-6 secretion compared to control (P < 0.05). Resveratrol can significantly promote the expression of SIRT1 in BMSCs of inflammation group, promote cell proliferation, decrease Caspase 3 activity, and increase Runx2 and OC expression. In addition, it decreased PPARγ2 and NF-κB expression and reduced the secretion of TNF-α and IL-6 (P < 0.05). The expression of SIRT1 was decreased in BMSCs under inflammation. SIRT1 overexpression in BMSCs under inflammation inhibits inflammation, promotes proliferation and osteogenic differentiation of BMSCs through regulating NF-κB signaling pathway.

Exploring molecular mechanism of novel liposomal nanoparticles application in glioma

2021 ◽  
Vol 11 (7) ◽  
pp. 1161-1167
Author(s):  
Guo-Shi Lin ◽  
Song-Jie Tu ◽  
Shui-Shun Zheng ◽  
Wei-Wen Wang ◽  
Rui-Sheng Lin
Keyword(s):  
Cell Proliferation ◽  
Caspase 3 ◽  
Mrna Level ◽  
Glioma Cells ◽  
Glioma Cell Line ◽  
Control Group ◽  
Targeted Nanoparticles ◽  
Reduce Cell Proliferation ◽  
Liposomal Nanoparticles ◽  
Tissue Specimens

This study investigated whether miR-509 plays a role in regulating autophagy and apoptosis-related caspase 3 genes, and analyzes targeted nanoparticles intervention in glioma cells. The surgically resected glioma tissue specimens were included as observation group, and control group used a 2-cm open tissue next to the glioma followed by analysis of miR-509 and caspase 3 level by qPCR. Glioma cell line U251 was divided into miRNC group, targeted nanoparticle group, siRNA-NC group, and siRNA-caspase 3 group, followed by analysis of caspase 3 expression, cell proliferation by flow cytometry, and cell invasion and metastasis by trans well. Caspase 3 mRNA expression was significantly higher in glioma tissues compared with controls. Lower miR-509 and higher caspase 3 expression were correlated with TNM stage. Caspase 3 mRNA level was significantly higher and miR-509 was lower in glioma cells or glioma ell line U251 than those in normal cells. Transfection of siRNA-caspase 3, targeted nanoparticles effectively reduced cell proliferation, metastasis, and invasion and down-regulated caspase 3 levels in U251 cells. Reduced miR-509 expression was associated with elevated caspase 3 expression and enhanced invasive metastatic capacity of glioma cells. Overexpression of miR-509 can effectively reduce cell proliferation, metastasis, and invasion by targeted nanoparticles inhibiting caspase 3 expression.

MiR-532-3p Suppresses Nucleus Pulposus Cells Proliferation and Extracellular Matrix Production, Promotes Cell Apoptosis via Targeting High Mobility Group AT-Hook 2

2021 ◽  
Vol 11 (7) ◽  
pp. 1313-1319
Author(s):  
Zhisheng Long ◽  
Feipeng Gong ◽  
Chen Li
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
High Mobility ◽  
High Mobility Group ◽  
Luciferase Reporter ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Nucleus Pulposus Cells

The present study aimed to investigate the function and mechanism of microRNA (miR)-532-3p in intervertebral disc degeneration (IDD). Further, whether miR-532-3p regulates HMGA2 in nucleus pulposus (NP) cells was explored. We collected human nucleus pulposus (NP) tissues from the patients with IDD, and detected miR-532-3p in NP tissues using RT-qPCR. MiR-532-3p mimic and inhibitor were constructed, and they were transfected into the human nucleus pulposus cells (HNPCs) by Lipofectamine 3000. MTT assay was conducted to determine cell proliferation. Cell apoptosis and extracellular matrix remodeling were examined by flow cytometric, Caspase 3/8 Assay Kits and Western blot. A dual-luciferase reporter assay was applied to investigate whether miR-532-3p targets High mobility group AT-hook 2 (HMGA2). We found miR-532-3p expression level was significantly increased in NP tissues of IDD patients, comparing with the controls. MiR-532-3p exerted an inhibitory effect on HNPCs proliferation; however, cell apoptosis and the degradation of extracellular matrix were induced by miR-532-3p. MiR-532-3p directly targets HMGA2, and HMGA2 overexpression reversed the role of miR-532-3p mimic in HNPCs proliferation, apoptosis, and extracellular matrix remodeling. Our study is the first to report that miR-532-3p might suppress NP cell proliferation, promote cell apoptosis and inhibit ECM production of NP cells via targeting HMGA2, thus facilitating the progression of IDD. MiR-532-3p was supposed to be a novel target for the treatment of IDD.

Effect of 25-Hydroxycholesterol on the Differentiation of Bone Marrow Mesenchymal Stem Cells Through Wnt5/TGF-β Signaling Pathway

2019 ◽  
Vol 9 (11) ◽  
pp. 1583-1588
Author(s):  
Shaoting Li ◽  
Jinhe Zhou ◽  
Zhiqing Ye ◽  
Shenglin Wu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Control Group ◽  
Nodule Formation ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) can be multi-directionally differentiated and are widely used in tissue engineering. 25-hydroxycholesterol (25-HC) can induce osteogenesis and is involved in osteogenic formation. However, the role of 25-hydroxycholesterol in BMSCs is unclear. Rat BMSCs were isolated and divided into control group and 25-HC treatment (2 and 4 μM) group. Cell proliferation was detected by MTT assay. Caspase-3 and ALP activity was analyzed. Real time PCR was done to analyze Runx2, OPN, FABP4 and PPARγ2 expression. Red staining detects the calcified nodule formation. Wnt5 level was detected by western blot and TGF-β secretion was analyzed by ELISA. 25-HC treatment significantly inhibited cell proliferation, increased Caspase 3 activity, decreased ALP activity and the expression of Runx2 and OPN, increased expression of FABP4 and PPARγ2, decreased formation of calcified nodules, secretion of TGF-β and reduced expression of Wnt5 compared to control group (P < 0.05), and the above changes were significant with the increase of the concentration of 25-HC (P < 0.05). 25-hydroxycholesterol regulates the proliferation and apoptosis of BMSCs by regulating Wnt5/TGF-β signaling pathway, inhibiting the differentiation of BMSCs into osteogenic direction and promoting its adipogenic differentiation.

miR-34 Promotes Autophagy and Apoptosis of Spinal Chondrocytes by Mammalian Target of Rapamycin/Phosphatidylinositol-3-Kinase/Protein Kinase B Signaling

2020 ◽  
Vol 10 (12) ◽  
pp. 1877-1883
Author(s):  
Jun Wu ◽  
Fenfen Zhao ◽  
Feng Tian ◽  
Feng Ma ◽  
Tao Guan
Keyword(s):  
Cell Proliferation ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Articular Chondrocyte

Autophagy and apoptosis of chondrocytes participate in spondyloarthritis (SpA). miR-34 involves in various diseases. However, miR-34’s role in autophagy and apoptosis of spine chondrocytes remains unclear. SpA patients and normal bone and articular cartilage tissues were collected, and miR-34 level was detected by Real-time PCR. The chondrocytes of SpA patients were isolated and divided into control group, miR-34 siRNA group and miR-34 group followed by analysis of Caspase 3 activity, cell proliferation by MTT assay, expression of Bax, Bcl-2, ATG5 and Beclin1 by Real time PCR, mTOR/PI3K/AKT signaling pathway protein expression by western blot, as well as TNF-α and IL-6 secretion by ELISA. miR-34 was significantly upregulated in SpA patients compared to normal (P <0.05). miR-34 siRNA transfection into SpA chondrocytes significantly down-regulated miR-34 expression, promoted cell proliferation, decreased Caspase 3 activity and Bax expression, increased Bcl-2, ATG5 and Beclin1 expression, decreased TNF-α and IL- 6 secretion as well as increased pmTOR and pAKT expression (P <0.05). miR-34 mimics was transfected into SpA chondrocytes, which up-regulated miR-34 expression and significantly reversed the above changes (P <0.05). miR-34 is upregulated in SpA patients. Down-regulation of miR-34 inhibits articular chondrocyte apoptosis and promotes autophagy by down-regulatingmTOR/PI3K/AKT signaling pathway, thereby promoting articular chondrocyte proliferation and inhibiting joint inflammation.

scholarly journals Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Xiao-Jing Li ◽  
Zhi-Feng Li ◽  
Jiu-Jiang Wang ◽  
Zhao Han ◽  
Zhao Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Normal Skin ◽  
Negative Control ◽  
Migration And Invasion ◽  
Caspase 9 ◽  
P53 Signaling ◽  
P53 Signaling Pathway ◽  
Skin Samples

The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 α (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA–Gadd45a, and miR-374 inhibitors + siRNA–Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA–Gadd45a group showed decreased miR-374 level; the siRNA–Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a.

scholarly journals Protective Effects of MicroRNA-126 on Human Cardiac Microvascular Endothelial Cells Against Hypoxia/Reoxygenation-Induced Injury and Inflammatory Response by Activating PI3K/Akt/eNOS Signaling Pathway

2017 ◽  
Vol 42 (2) ◽  
pp. 506-518 ◽  
Author(s):  
Hong-Hui Yang ◽  
Yan Chen ◽  
Chuan-Yu Gao ◽  
Zhen-Tian Cui ◽  
Jian-Min Yao
Keyword(s):  
Cell Proliferation ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Control Group ◽  
Protective Effects ◽  
Enos Expression ◽  
Lumen Formation ◽  
Tnf Α ◽  
Cardiac Microvascular Endothelial Cells

Objective: This study explored the protective effects of the microRNA-126 (miR-126)-mediated PI3K/Akt/eNOS signaling pathway on human cardiac microvascular endothelial cells (HCMECs) against hypoxia/reoxygenation (H/R)-induced injury and the inflammatory response. Methods: Untreated HCMECs were selected for the control group. After H/R treatment and cell transfection, the HCMECs were assigned to the H/R, miR-126 mimic, mimic-negative control (NC), miR-126 inhibitor, inhibitor-NC, wortmannin (an inhibitor of PI3K) and miR-126 mimic + wortmannin groups. Super oxide dismutase (SOD), nitric oxide (NO), vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) were measured utilizing commercial kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to detect miR-126 expression and the mRNA and protein expression of inflammatory factors. Western blotting was used to determine the expression of key members in the PI3K/Akt/eNOS signaling pathway. ACCK-8 assay and flow cytometry were employed to examine cell proliferation and apoptosis, respectively. The angiogenic ability in each group was detected by the lumen formation test. Results: Compared to the control group, p/t-PI3K, p/t-Akt and p/t-eNOS expression, NO, VEGF and SOD levels, cell proliferation and in vitro lumen formation ability were decreased, while the ROS content, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α expression and cell apoptosis were significantly increased in the H/R, mimic-NC, miR-126 inhibitor, inhibitor-NC, wortmannin and miR-126 mimic + wortmannin groups. Additionally, in comparison with the H/R group, the miR-126 mimic group had elevated p/t-PI3K, p/t-Akt and p/t-eNOS expression, increased NO, VEGF and SOD contents, and strengthened cell proliferation and lumen formation abilities but also exhibited decreased ROS content, reduced IL-6, IL-10 and TNF-α expressions, and weakened cell apoptosis, while the miR-126 inhibitor and wortmannin group exhibited the opposite results. Furthermore, decreased p/t-PI3K, p/t-Akt and p/t-eNOS expressions, decreased NO, VEGF and SOD contents, cell proliferation and lumen formation abilities, as well as increased ROS content, increased IL-6, IL-10 and TNF-α expression, and increased cell apoptosis were observed in the miR-126 mimic + wortmannin group compared to themiR-126 mimic group. Conclusions: These findings indicated that miR-126 protects HCMECs from H/R-induced injury and inflammatory response by activating the PI3K/Akt/ eNOS signaling pathway.

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