scholarly journals CircSETDB1 knockdown inhibits the malignant progression of serous ovarian cancer through miR-129-3p-dependent regulation of MAP3K3

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Bo Li ◽  
Lu Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Therapeutic Target ◽  
Tumor Formation ◽  
Malignant Progression ◽  
Cell Counting ◽  
Serous Ovarian Cancer ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Circular RNA (circRNA) is recently found to participate in the regulation of tumor progression, including ovarian cancer. However, the application of circRNA SET domain bifurcated histone lysine methyltransferase 1 (circSETDB1) as a therapeutic target in serous ovarian cancer (SOC) remains to be elucidated. Herein, circSETDB1 role in SOC malignant progression and underlying mechanism are revealed. Methods The expression of circSETDB1, microRNA-129-3p (miR-129-3p) and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) messenger RNA (mRNA) was detected by quantitative real-time polymerase chain reaction. Protein abundance was determined by western blot analysis. Cell proliferation, apoptosis, invasion and migration were demonstrated by cell counting kit-8 and 5-Ethynyl-29-deoxyuridine assays, flow cytometry analysis, transwell invasion assay and wound-healing assay, respectively. The interaction between miR-129-3p and circSETDB1 or MAP3K3 was predicted by online database, and identified by mechanism assays. The effect of circSETDB1 knockdown on tumor formation in vivo was unveiled by mouse model experiment. Results CircSETDB1 and MAP3K3 expression were apparently upregulated, whereas miR-129-3p expression was downregulated in SOC tissues and cells in comparison with normal fallopian tube tissues or normal ovarian epithelial cells. CircSETDB1 knockdown inhibited cell proliferation, invasion and migration, but induced cell apoptosis in SOC cells. Additionally, miR-129-3p inhibitor impaired circSETDB1 silencing-mediated SOC malignant progression. MiR-129-3p repressed SOC cell processes via binding to MAP3K3. Furthermore, circSETDB1 knockdown suppressed tumor growth in vivo. Conclusion CircSETDB1 silencing repressed SOC malignant progression through miR-129-3p/MAP3K3 pathway. This study supports circSETDB1 as a new therapeutic target for SOC.

scholarly journals Circ_0061140 knockdown inhibits tumorigenesis and improves PTX sensitivity by regulating miR-136/CBX2 axis in ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jun Zhu ◽  
Jun-e Luo ◽  
Yurong Chen ◽  
Qiong Wu
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Tumor Formation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Diphenyltetrazolium Bromide ◽  
Polymerase Chain

Abstract Background Ovarian cancer is an aggressive tumor in women with high mortality. Paclitaxel (PTX) can be used for the chemotherapy of ovarian cancer. Here, the roles of circular_0061140 (circ_0061140) in PTX sensitivity and malignant progression of ovarian cancer are unveiled. Methods The expressions of circ_0061140, microRNA-136 (miR-136) and chromobox 2 (CBX2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot. The half maximal inhibitory concentration (IC50) of PTX was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was investigated by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by transwell assay. The binding relationship between miR-136 and circ_0061140 or CBX2 was predicted by interactome or starbase online database, and identified by dual-luciferase reporter assay. The effects of circ_0061140 on tumor formation and PTX sensitivity in vivo were disclosed by tumor formation assay. Results Circ_0061140 and CBX2 expressions were upregulated, while miR-136 expression was downregulated in PTX-resistant tissues and cells compared with control groups. Circ_0061140 knockdown repressed cell proliferation, migration and invasion, and promoted cell apoptosis and PTX sensitivity; however, these effects were restrained by miR-136 RNAi. Additionally, circ_0061140 was a sponge of miR-136, and miR-136 bound to CBX2. Furthermore, circ_0061140 knockdown inhibited tumor formation and improved PTX sensitivity in vivo. Conclusions Circ_0061140 silencing repressed the progression and PTX resistance of ovarian cancer by downregulating CBX2 expression via sponging miR-136, which provided novel insight into studying the therapy of ovarian cancer with PTX.

scholarly journals Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wumei Lin ◽  
Haiyan Ye ◽  
Keli You ◽  
Le Chen
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Ovarian cancer (OC) is a common fatal malignant tumor of female reproductive system worldwide. Growing studies have proofed that circular RNAs (circRNAs) engage in the regulation of various types of cancers. However, the underlying biological functions and effect mechanism of circular RNA_LARP4 (circ_LARP4) in OC have not been explored. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect the expression of circ_LARP4 in OC cells. The function of circ_LARP4 was measured by cell counting kit-8 (CCK-8), colony formation assay and transwell assay. RNA immunoprecipitation (RIP) assay and luciferase reporter assays assessed the binding correlation between miR-513b-5p and circ_LARP4 (or LARP4). Results The expression of circ_LARP4 in OC cells was much lower than that in human normal ovarian epithelial cells. Overexpressing circ_LARP4 impaired cell proliferation, invasion and migration abilities. Circ_LARP4 worked as a competing endogenous RNA (ceRNA) to sponge miR-513b-5p. Furthermore, LARP4 was indirectly modulated by circ_LARP4 as the downstream target of miR-513b-5p, as well as the host gene of circ_LARP4. Conclusion Circ_LARP4 could hamper cell proliferation and migration by sponging miR-513b-5p to regulate the expression of LARP4. This research may provide some referential value to OC treatment.

scholarly journals microRNA-4488 in extracellular vesicles derived from marrow mesenchymal stem cells suppresses ABHD8 to inhibit ovarian cancer progression

2020 ◽  
Author(s):  
Lei Chang ◽  
Junying Zhou ◽  
Wanjia Tian ◽  
Mengyu Chen ◽  
Ruixia Guo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Extracellular vesicle (EV) that delivered microRNAs (miRNAs) have been found as the important biomarkers participating in the pathological mechanism of ovarian cancer. Consequently, this study sought to examine the underlying mechanism of mesenchymal stem cell (MSC)-derived EVs containing miR-4488 in ovarian cancer. Methods The normal ovarian tissues and ovarian cancer tissues were extracted, and the information of MSC-EV miRNA was obtained by Bioinformatics analysis. RT-qPCR and western blot analysis were applied to detect miR-4488 and α/β-hydrolase domain-containing (ABHD)8 expression followed by determination of relationship between miR-4488 and ABHD8 by dual-luciferase reporter assay. After transfection with different plasmids and treatment with DMSO or GW4869 (inhibitor of EV), the regulatory roles of MSC-EV-miR-4488 in invasion, proliferation, apoptosis, and migration of cancer cells were explored. Besides, xenograft tumor in nude mice was conducted to explore the role of miR-4488 and ABHD8 in ovarian cancer in vivo. Results miR-4488 was poorly expressed and ABHD8 was highly expressed in ovarian cancer cells and tissues. ABHD8 was a target gene of miR-4488 while the knockdown of ABHD8 resulted in the suppression of proliferation, invasion, and migration while promoting the apoptosis of cancer cells. Functionally, MSC-EV-derived miR-4488 inhibited the expression of ABHD8. Additionally, miR-4488 over-expressed in MSC-EVs inhibited the cell proliferation, invasion, and migration through down-regulation of ABHD8 expression. At last, these in vitro findings were also confirmed in vivo. Conclusion To summarize, miR-4488 overexpressed in MSC-EVs suppressed ABHD8 expression to inhibit the cancer cell proliferation, invasion, and migration, thus suppressing ovarian cancer.

scholarly journals Hsa_circ_0004712 downregulation attenuates ovarian cancer malignant development by targeting the miR-331-3p/FZD4 pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xuan Zhou ◽  
Jinchi Jiang ◽  
Shuaishuai Guo
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Colony Formation ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Circular Rnas ◽  
Action Mechanism ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Circular RNAs (circRNAs) are gradually reported to be implicated in the development of malignant tumors, including ovarian cancer (OC). This paper intended to explore the function and action mechanism of hsa_circ_0004712 in OC. Results In our results, hsa_circ_0004712 was aberrantly overexpressed in OC tissues and cells. Downregulation of hsa_circ_0004712 impaired OC cell proliferation, colony formation, invasion and migration, and accelerated apoptosis. Hsa_circ_0004712 directly targeted miR-331-3p whose inhibitors reversed the effects of hsa_circ_0004712 downregulation. FZD4 was targeted by miR-331-3p, and hsa_circ_0004712 could positively regulated FZD4 expression by targeting miR-331-3p. The anti-tumor effects of miR-331-3p restoration were reversed by FZD4 overexpression. Downregulation of hsa_circ_0004712 also impaired tumor development in vivo by regulating miR-331-3p and FZD4. Conclusion In conclusion, hsa_circ_0004712 deficiency repressed OC development by mediating the miR-331-3p/FZD4 pathway, predicting that hsa_circ_0004712 was a promising biomarker for OC diagnosis and therapy.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoling Liu ◽  
Chenyu Wang ◽  
Qing Yang ◽  
Yue Yuan ◽  
Yunjian Sheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Biological Function ◽  
Cell Metabolism ◽  
Hub Genes ◽  
Invasion And Migration ◽  
And Migration

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

miR-216a-5p Suppresses the Proliferation, Invasion and Migration of Fibroblast-Like Synoviocyte in Rheumatoid Arthritis by Targeting Zinc Finger and BTB Domain-Containing Protein 2 (ZBTB2)

2021 ◽  
Vol 11 (5) ◽  
pp. 896-902
Author(s):  
Jinwei Zhao ◽  
Ling Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Zinc Finger ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Healthy Controls ◽  
Invasion And Migration ◽  
Btb Domain ◽  
And Migration

MicroRNAs have been reported to be associated with the initiation and progression of rheumatoid arthritis (RA). miR-216a-5p, one of the miRNAs, is involved in cancer cell proliferation, invasion and migration. However, the role of miR-216a-5p in RA remains to be explored. The expressions of miR-216a-5p and zinc finger and BTB domain-containing protein 2 (ZBTB2) in fibroblast-like synoviocytes (FLS) of RA or healthy controls were detected by qRT-PCR and western blot analysis. Transfection of overexpressed and silenced miR-216a-5p were performed to explore the functional role of miR-216a-5p in RA-FLS. Cell Counting Kit-8 (CCK-8) assay and transwell assay were employed to assess cell proliferation and cell invasion, respectively. Moreover, luciferase reporter assay was executed to verify the combination of miR-216a-5p and ZBTB2. The results showed that miR-216a-5p expression in RA-FLS was downregulated than healthy controls. Overexpres-sion of miR-216a-5p inhibited RA-FLS cell proliferation, invasion and migration, while miR-216a-5p silencing revealed the opposite results. In addition, ZBTB2 was identified to be a direct target of miR-216a-5p in RA-FLS and its expression was higher than that in healthy controls. Rescue experiments revealed that ZBTB2 overexpression reversed the effects of miR-216a-5p on the proliferation, invasion and migration of RA-FLS. These data indicated the suppressive role of miR-216a-5p in RA-FLS via the regulation of ZBTB2, suggesting that miR-216a-5p and ZBTB2 may be the new targets for the treatment of RA.

scholarly journals STK3 Suppresses Ovarian Cancer Progression by Activating NF-κB Signaling to Recruit CD8+ T-Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Xiangyu Wang ◽  
Fengmian Wang ◽  
Zhi-Gang Zhang ◽  
Xiao-Mei Yang ◽  
Rong Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
T Cells ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Gene Set Enrichment Analysis ◽  
Ovarian Cancer Cells ◽  
And Migration

Serine/threonine protein kinase-3 (STK3) is a critical molecule of the Hippo pathway but little is known about its biological functions in the ovarian cancer development. We demonstrated the roles of STK3 in ovarian cancer. Existing databases were used to study the expression profile of STK3. STK3 was significantly downregulated in OC patients, and the low STK3 expression was correlated with a poor prognosis. In vitro cell proliferation, apoptosis, and migration assays, and in vivo subcutaneous xenograft tumor models were used to determine the roles of STK3. The overexpression of STK3 significantly inhibited cell proliferation, apoptosis, and migration of ovarian cancer cells in vitro and tumor growth in vivo. Bisulfite sequencing PCR analysis was performed to validate the methylation of STK3 in ovarian cancer. RNA sequencing and gene set enrichment analysis (GSEA) were used to compare the transcriptome changes in the STK3 overexpression ovarian cancer and control cells. The signaling pathway was analyzed by western blotting. STK3 promoted the migration of CD8+ T-cells by activating nuclear transcription factor κB (NF-κB) signaling. STK3 is a potential predictor of OC. It plays an important role in suppressing tumor growth of ovarian cancer and in chemotaxis of CD8+ T-cells.

Nobiletin Inhibits Proliferation, Invasion, Migration and Angiogenesis in Colorectal Cancer Cells

2019 ◽  
Vol 9 (5) ◽  
pp. 662-667
Author(s):  
Jing Li ◽  
Zaijun Li ◽  
Fei Zheng
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Human Cancer ◽  
Cell Counting ◽  
Control Group ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Traditional Chinese Herbal Medicine ◽  
And Migration

Aim/Background: The nobiletin is a polymethoxyflavonoid isolated from citrus, which is a traditional Chinese herbal medicine. The nobiletin could inhibit the development of human cancer. However, the role of nobiletin in human colorectal cancer (CRC) remains unknown. The present study aimed to explore the nobiletin function in CRC cell proliferation, migration, invasion and angiogenesis as well as the occurrence mechanisms. Methods: The cell counting kit-8 assay (CCK-8 assay) and Brdu (5-brom-2-odeoxyuridine) staining assay were used to determine the effect of nobiletin on cell proliferation. The transwell assay and wound healing assay were used to assess cell invasion and migration. The western blot analysis was performed to determine the expression of VEGFA, Ang2, p65, p-p65, STAT3, p-STAT3 in CRC cell. Result: Compared with the control group (0 mg/L), the cell proliferation was increased in a dose-dependent manner with 10, 50, 100, 150 mg/L nobiletin for 48 h. The nobiletin inhibited cell invasion and migration and suppressed the expression of VEGFA and Ang2 to block angiogenesis in the colorectal cancer. In addition, we found that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis by suppression of NF-κB/STAT3 pathway. Conclusion: The study provided evidence that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis in the colorectal cancer.

scholarly journals MiR-18a-5p Promotes NPC Cell Proliferation, Invasion, Migration, and EMT by Targeting SMAD2

2020 ◽  
Author(s):  
Pengcheng Li ◽  
Junhui Xing ◽  
Jianwu Jiang ◽  
Xinyu Tian ◽  
Xuemeng Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Invasion And Migration ◽  
Metastasis Model ◽  
And Migration ◽  
Dual Luciferase Reporter Assay

Abstract Background: Nasopharyngeal carcinoma (NPC) is the most common malignant tumor in the head and neck that is characterized by high local malignant invasion and distant metastasis. miR-18a-5p reportedly plays an important role in tumorigenesis and development. However, little is known about the mechanism underlying miR-18a-5p’s role in NPC.Methods：Quantitative real-time PCR was used to detect the expression of miR-18a-5p in NPC tissues and cell lines. MTT assay and plate clone formation assay were used to detect the effect of miR-18a-5p on NPC cell proliferation. Woundhealing assays and Transwell assays were used to detect the effect of miR-18a-5p on NPC cell invasion and migration. The expressions of epithelialmesenchymal transition (EMT)-related proteins N-cadherin, Vimentin, and E-cadherin were detected by Westernblot. Bioinformatics and dual-luciferase reporter assay were used to detect the targeting interaction between miR-18a-5p and SMAD2. Xenotransplantation and metastasis model were used to detect the effect of miR-18a-5p on NPC growth and metastasis in vivo.Results:miR-18a-5p was highly expressed in NPC tissues and cell lines. Overexpression of miR-18a-5p promotedNPC cell proliferation, invasion, migration, and EMT process, whereas inhibition of miR-18a-5p expression led to the oppositeresults. Results of dual-luciferase reporter assay showed that SMAD2 was the target gene of miR-18a-5p, and SMAD2 could reverse the effect of miR-18a-5p on NPC cell line. Xenotransplantation and metastasis model experiments in nude mice showed that miR-18a-5p promotesNPC growth and metastasis in vivo.Conclusions:Targeting SMAD2 downregulated miR-18a-5p expression, thereby promoting NPC cell proliferation, invasion, migration, and EMT.

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