scholarly journals MicroRNA-361-5p Inhibits Tumorigenesis and the EMT of HCC by Targeting Twist1

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Liang-Chun Yin ◽  
Gang Xiao ◽  
Rui Zhou ◽  
Xiao-Ping Huang ◽  
Ning-Lei Li ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Suppressive Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition ◽  
Reporter Assays

MicroRNA-361-5p (miR-361-5p) is a tumor suppressor miRNA that is dysregulated in several types of human cancer. However, the functional significance of miR-361-5p in hepatocellular carcinoma (HCC) is unclear. This study explored the biological function of miR-361-5p in regulating the progression of HCC and the underlying molecular mechanism. RT-qPCR analysis showed that miR-361-5p was downregulated in HCC tissues and cell lines. Functional analysis revealed that miR-361-5p acted as a tumor suppressor, inhibiting cell proliferation, migration, and invasion in HCC cell lines. Bioinformatics analyses identified Twist1 as a direct target of miR-361-5p, which was validated by dual-luciferase reporter assays, RT-qPCR, and western blotting. Rescue experiments indicated that Twist1 may mediate the tumor-suppressive effect of miR-361-5p in HCC cells, and this was supported by the effect of miR-361-5p on inhibiting the epithelial-mesenchymal transition (EMT) by targeting Twist1. This study is the first to suggest that miR-361-5p inhibits tumorigenesis and EMT in HCC by targeting Twist1. These findings are valuable for the diagnosis and clinical management of HCC.

scholarly journals Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 921-931
Author(s):  
Juan Zhao ◽  
Xue-Bin Zeng ◽  
Hong-Yan Zhang ◽  
Jie-Wei Xiang ◽  
Yu-Song Liu
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractLong non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.

Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway

2021 ◽  
Vol 53 (4) ◽  
pp. 481-491
Author(s):  
Lizhi Lin ◽  
Jialiang Wen ◽  
Bangyi Lin ◽  
Hao Chen ◽  
Adheesh Bhandari ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phospholipase C ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Suppressive Effect ◽  
The Cancer Genome Atlas ◽  
Disease Stage ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

scholarly journals microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Dawei Wang ◽  
Guoliang Lu ◽  
Yuan Shao ◽  
Da Xu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial–mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected using MTT assay, and cell apoptosis was evaluated using flow cytometry. Transwell assay was conducted to investigate cell migration and invasion. Expression analysis of a set of EMT markers was performed to explore whether miR-802 is involved in EMT program. Xenograft model was established to investigate the function of miR-802 in carcinogenesis in vivo. The direct regulation of Flotillin-2 (Flot2) by miR-802 was identified using luciferase reporter assay. miR-802 was remarkably down-regulated in PCa tissues and cell lines. Gain-of-function trails showed that miR-802 serves as an ‘oncosuppressor’ in PCa through inhibiting cell proliferation and promoting cell apoptosis in vitro. Overexpression of miR-802 significantly suppressed in vivo PCa tumor growth. Luciferase reporter analysis identified Flot2 as a direct target of miR-802 in PCa cells. Overexpressed miR-802 significantly suppressed EMT, migration and invasion in PCa cells by regulating Flot2. We identified miR-802 as a novel tumor suppressor in PCa progression and elucidated a novel mechanism of the miR-802/Flot2 axis in the regulation of EMT, which may be a potential therapeutic target.

scholarly journals A transcription factor that promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of ovarian cancer cells and its possible mechanisms

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yingying Qi ◽  
Kexin Mo ◽  
Ting Zhang
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
High Morbidity ◽  
Mesenchymal Transition ◽  
Gata3 Expression

Abstract Background Ovarian cancer is one of the most common gynecological malignancies with the high morbidity and mortality. This study was aimed to explore the role of non-structure maintenance of chromosomes condensin I complex subunit H (NCAPH) in the progression of ovarian cancer (OC) and the transcription regulatory effects of GATA binding protein 3 (GATA3) on this gene. Methods Firstly, NCAPH and GATA3 expression in OC tissues and several human OC cell lines was, respectively, evaluated by TNMplot database and Western blot analysis. Then, NCAPH was silenced to assess the proliferation, migration, and invasion of OC cells in turn using CCK-8, wound healing, and transwell assays. Western blotting was used to determine the expression of epithelial--mesenchymal transition (EMT)-related proteins and PI3K/PDK1/AKT signaling proteins. The potential binding sites of GATA3 on NCAPH promoter were predicated using JASPAR database, which were verified by luciferase reporter assay and chromosomal immunoprecipitation. Subsequently, GATA3 was overexpressed to examine the biological functions of OC cells with NCAPH silencing. Results NCAPH and GATA3 expression was significantly upregulated in OC tissues and cell lines. NCAPH loss-of-function notably inhibited the proliferation, migration, invasion, and EMT of OC cells. Moreover, the expression of p-PI3K, PDK1, and p-AKT was downregulated after NCAPH knockdown. Furthermore, GATA3 was confirmed to bind to NCAPH promoter. GATA3 overexpression alleviated the inhibitory effects of NCAPH silencing on the proliferation, migration, invasion, EMT, and expression of proteins in PI3K/PDK1/AKT pathway of OC cells. Conclusion To sum up, NCAPH expression transcriptional activation by GATA3 accelerates the progression of OC via upregulating PI3K/PDK1/AKT pathway.

scholarly journals Long Non-Coding RNA RP11-789C1.1 Suppresses Epithelial to Mesenchymal Transition in Gastric Cancer Through the RP11-789C1.1/MiR-5003/E-Cadherin Axis

2018 ◽  
Vol 47 (6) ◽  
pp. 2432-2444 ◽  
Author(s):  
Zehong Chen ◽  
Jialin Wu ◽  
Wensheng Huang ◽  
Jianjun Peng ◽  
Jinning Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Epithelial To Mesenchymal Transition ◽  
Cellular Level ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Reporter Assays ◽  
E Cadherin

Background/Aims: Gastric cancer (GC) is a common malignancy with a global incidence that ranks fourth among all tumor types. Epithelial-to-mesenchymal transition (EMT) is a tumor biological process with a role in GC cell metastasis. Long non-coding RNAs (lncRNAs) and microRNAs possess important regulatory functions at the cellular level and in diverse pathophysiological processes. This study was conducted to investigate whether lncRNA RP11-789C1.1 regulates EMT in GC by mediating the miR-5003/E-cadherin pathway. Methods: RP11-789C1.1 and miR-5003 expression was detected in GC specimens and cell lines by quantitative real-time PCR. Western blotting and immunohistochemistry were performed to detect EMT markers in GC. Cell Counting Kit 8 assays were carried out to explore cell proliferation. Wound healing and Transwell assays were conducted to determine the migration and invasion of GC cells. To clarify the correlation between RP11-789C1.1, miR-5003, and E-cadherin, dual-luciferase reporter assays were applied. Results: LncRNA RP11-789C1.1 was significantly down-regulated in GC patients and cell lines, along with the concomitant up-regulation of miR-5003. Silencing RP11-789C1.1 and over-expressing miR-5003 significantly promoted the tumor behavior of GC cells. Dual-luciferase reporter assays confirmed that miR-5003 was the target of both RP11-789C1.1 and E-cadherin. Furthermore, at both the mRNA and protein level, silencing RP11-789C1.1 remarkably reduced the expression of E-cadherin and promoted EMT, which were reversed by knocking down miR-5003. Conclusions: LncRNA RP11-789C1.1 inhibited EMT in GC through the RP11-789C1.1/miR-5003/E-cadherin axis, which could be a promising therapeutic target for GC.

scholarly journals MiR-15a-5p Inhibits Migration and Invasion of Ovarian Cancer Cells by Targeting PELP1

2020 ◽  
Author(s):  
Yujia Yang ◽  
Li Yuan ◽  
Bing Yang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Mesenchymal Transition ◽  
Reporter Assays

Abstract Background: Ovarian cancer is one of the most common malignancy of the female reproductive system. Hsa‐miR‐15a‐5p (miR‐15a-5p) has been reported with tumor‐suppressing roles in various cancers. This study aims to determine the role of miR-15a-5p during the progression of ovarian cancer. Methods: We used bioinformatics, luciferase reporter assays, wound-healing, transwell invasion assays, quantitative Real-time polymerase chain reaction (qRT-PCR) and Western blot to dissect the molecular mechanism of how miR-15a-5p may cause metastasis in ovarian cancer. Results: The upregulation of miR‐15a-5p inhibited growth, migration and invasion in ovarian cancer cells. Furthermore, miR-15a-5p suppressed epithelial mesenchymal transition (EMT) of ovarian cancer cell in vitro, evidenced by expression alteration of E‐cadherin and vimentin. Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) was identified as the direct target of miR-15a-5p and downregulated by miR-15a-5p. The inhibitory effect of miR-15a-5p on migration, invasion and EMT was rescued by PELP1. Additionally, downregulation of PELP1 mimicked the suppressive impact of miR-15a-5p on ovarian carcinoma cells. Conclusions: Our data indicated that miR-15a-5p inhibited migration, invasion and EMT of ovarian cancer cells by targeting PELP1, which might relate to the progression and metastasis of ovarian cancer.

scholarly journals Angio-Associated Migratory Cell Protein (AAMP) Regulates the Hippo/YAP Pathway and Mitochondrial Functionality to Drive Osteosarcoma Metastasis

2022 ◽  
Author(s):  
Fangbiao Zhan ◽  
Zhiyu Chen ◽  
Chaozheng Xie ◽  
Shuang Xiang ◽  
Qianrong Deng ◽  
...  
Keyword(s):  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Characteristics ◽  
Cellular Migration ◽  
Cell Protein ◽  
Migration And Invasion ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition ◽  
Cell Protrusion ◽  
Migratory Cell

Abstract Background: Osteosarcoma (OS) is the prevalent form of primary bone cancer among adolescents, but the 5-year overall survival rate for patients with a metastatic or recurrent OS is under 20%. Angio-associated migratory cell protein (AAMP) is known to be a key regulator of cellular migration, yet its role in the context of OS metastasis has yet to be firmly established.Methods: Bioinformatics analyses were used to explore the association between AAMP and YAP expression and the prognosis of OS patients, and to evaluate differences in AAMP expression in patients with primary OS, recurrent OS, and pulmonary metastatic OS. Immunohistochemical (IHC) staining was additionally performed to compare AAMP levels in primary OS and pulmonary metastatic OS patient samples. Lentiviral transduction was further used to establish OS cell lines in which AAMP or YAP had been stably knocked down or overexpressed. OS cell migration and invasion were assessed using wound healing and Transwell assays. Proteins associated with the mitochondria, the epithelial-mesenchymal transition (EMT), YAP, and its target proteins were assessed in OS cell lines via Western blotting. OS cell lamellipodia were detected via phalloidin staining. Mitochondrial morphological characteristics were assessed via transmission electron microscopy following the knockdown of AAMP. An ATP kit was employed to measure ATP levels in OS cells in which AAMP had been knocked down. Animal model studies were used to confirm indices associated with OS cell lung metastasis following AAMP knockdown. Results: Patients with metastatic OS exhibit higher levels of AAMP expression that are correlated with poorer patient prognosis. Knocking down AAMP suppressed the migratory, invasive, and EMT activity of analyzed OS cell lines. AAMP was found to regulate CFL1 and thereby control OS cell protrusion. AAMP knockdown was further found to promote OS cell mitochondrial dysfunction and decreased intracellular ATP production, with these AAMP knockdown cells exhibiting impaired migratory and invasive activity as a consequence of YAP inhibition. Consistently, the knockdown of AAMP suppressed the in vivo metastasis of OS cells. Conclusions: Together, these data highlight a model wherein AAMP can promote OS cell migratory and invasive activity by regulating YAP and mitochondrial functionality. The AAMP/CFL1/YAP signaling pathway may thus represent a viable therapeutic target for efforts aimed at suppressing the metastatic progression of OS.

scholarly journals MiR-877 suppresses gastric cancer progression by downregulating AQP3

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052090366 ◽  
Author(s):  
Hongyu Zhu ◽  
Yulian Wu ◽  
Muxing Kang ◽  
Bo Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Reporter Assays

Objectives Gastric cancer (GC) is the leading cause of cancer-related deaths worldwide; however, the underlying molecular mechanisms of GC remain unclear. This study investigated the role of the miR-877–AQP3 axis in GC tumorigenesis. Methods The levels of miR-877 expression were measured in GC tissues and cell lines by qRT-PCR. Functional assays were performed to elucidate the role of miR-877 in GC development. Results Our results showed that miR-877 levels were lower in GC tissues and cell lines compared with the corresponding controls. Additionally, reduced miR-877 levels were associated with unfavorable prognoses. Increased miR-877 expression suppressed proliferation, invasion, and epithelial-mesenchymal transition, while promoting apoptosis in GC cells. Luciferase reporter assays showed that aquaporin 3 (AQP3) was a direct downstream target of miR-877. Overexpression of AQP3 partially rescued the tumor suppressive effects of miR-877 in GC cells. Moreover, miR-877 was negatively correlated with AQP3 mRNA expression in GC tissues. Conclusions This study demonstrated that miR-877 plays a suppressive role in GC tumorigenesis by regulating AQP3.

scholarly journals Phosphoproteomic Profiling Identifies Aberrant Activation of Integrin Signaling in Aggressive Non-Type Bladder Carcinoma

2019 ◽  
Vol 8 (5) ◽  
pp. 703 ◽  
Author(s):  
Barnali Deb ◽  
Vinuth N. Puttamallesh ◽  
Kirti Gondkar ◽  
Jean P. Thiery ◽  
Harsha Gowda ◽  
...  
Keyword(s):  
Cell Lines ◽  
Bladder Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Subtype ◽  
Migration And Invasion ◽  
Bioinformatics Analyses ◽  
Mesenchymal Transition ◽  
Carcinoma Cell Lines ◽  
Liquid Chromatography Tandem Mass ◽  
Molecular Landscape

Bladder carcinoma is highly heterogeneous and its complex molecular landscape; thus, poses a significant challenge for resolving an effective treatment in metastatic tumors. We computed the epithelial-mesenchymal transition (EMT) scores of three bladder carcinoma subtypes—luminal, basal, and non-type. The EMT score of the non-type indicated a “mesenchymal-like” phenotype, which correlates with a relatively more aggressive form of carcinoma, typified by an increased migration and invasion. To identify the altered signaling pathways potentially regulating this EMT phenotype in bladder cancer cell lines, we utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based phosphoproteomic approach. Bioinformatics analyses were carried out to determine the activated pathways, networks, and functions in bladder carcinoma cell lines. A total of 3125 proteins were identified, with 289 signature proteins noted to be differentially phosphorylated (p ≤ 0.05) in the non-type cell lines. The integrin pathway was significantly enriched and five major proteins (TLN1, CTTN, CRKL, ZYX and BCAR3) regulating cell motility and invasion were hyperphosphorylated. Our study reveals GSK3A/B and CDK1 as promising druggable targets for the non-type molecular subtype, which could improve the treatment outcomes for aggressive bladder carcinoma.

scholarly journals MiRNA-206 suppresses PGE2-induced colorectal cancer cell proliferation, migration, and invasion by targetting TM4SF1

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Young Ran Park ◽  
Seung Young Seo ◽  
Se Lim Kim ◽  
Shi Mao Zhu ◽  
Sungkun Chun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Control Group ◽  
Mesenchymal Transition

MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC) cells through the targetting of transmembrane 4 L six family member 1 (TM4SF1).The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206.We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3′-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of β-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of p-AKT and p-ERK by targetting TM4SF1 in PGE2-induced cells.Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.

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