scholarly journals Knocking down of LINC01220 inhibits proliferation and induces apoptosis of endometrial carcinoma through silencing MAPK11

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yong Li ◽  
Chengcai Kong ◽  
Chaoying Wu ◽  
Yingqiao Wang ◽  
Boqun Xu ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Colony Formation ◽  
Function Analysis ◽  
Figo Stage ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Protein Coding ◽  
Gynecology And Obstetrics ◽  
Mitogen Activated Protein ◽  
Ec Cells

Abstract Background: Endometrial carcinoma (EC) still threatens the health of women. Thus, to explore how long intergenic non-protein coding RNA 01220 regulates the development of EC. Methods: Whole genome expression profile data of EC and paracancerous tissues in TCGA database were downloaded. LINC01220 expression in EC and paracancerous tissues of patients in our hospital were detected by qRT-PCR. Furthermore, the relationship between LINC01220 expression and clinicopathological features of EC patients was analyzed. After transfection with sh-LINC01220 and pcDNA-MAPK11 (mitogen-activated protein kinase) in EC cells, proliferative, colony formation abilities and apoptosis were determined by cell counting kit-8 (CCK-8), colony formation assay and flow cytometry, respectively. Western blot was conducted to determine the regulatory role of LINC01220 on MAPK11. Results: TCGA data showed that LINC01220 expression is markedly higher in EC tissues than that of paracancerous tissues, which was consistent without detection in EC patients of our hospital. LINC01220 expression was positively correlated to pathological grade and International Federation of Gynecology and Obstetrics (FIGO) stage of EC patients. After knockdown of LINC01220 in EC cells, proliferative and colony formation abilities decreased, whereas apoptotic rate increased. Cor function analysis revealed the positive correlation between LINC01220 and MAPK11 in EC. MAPK11 expression was regulated by LINC01220 in EC cells. Overexpression of MAPK11 can reverse the tumor suppressing effect of LINC01220 on EC. Conclusions: LINC01220 promotes EC development by stimulating proliferation and inhibiting apoptosis of EC cells through up-regulating MAPK11.

Claudin-1 is linked to presence of implants and micropapillary pattern in serous borderline epithelial tumours of the ovary

2018 ◽  
Vol 71 (12) ◽  
pp. 1060-1064 ◽  
Author(s):  
Ahmed El-Balat ◽  
Iryna Schmeil ◽  
Khayal Gasimli ◽  
Nicole Sänger ◽  
Thomas Karn ◽  
...  
Keyword(s):  
Figo Stage ◽  
Mitogen Activated Protein Kinase ◽  
Borderline Tumour ◽  
Peritoneal Implants ◽  
Gynecology And Obstetrics ◽  
Pathway Activation ◽  
Therapeutic Value ◽  
Mitogen Activated Protein ◽  
Epithelial Tumours ◽  
Micropapillary Pattern

AimsExpression of Claudin-1 has been associated with prognosis in several cancers. Here we investigated the expression pattern of Claudin-1 in borderline tumours of the ovary (BOT).MethodsWe analysed a cohort of 114 cases of borderline tumour (BOT). Claudin-1 expression was studied by immunohistochemistry using a polyclonal antibody and was compared with clinical and histopathological characteristics.ResultsStrong Claudin-1 expression was found in 30 cases (26.3%) independent of histological subtype. Expression was significantly less frequent in International Federation of Gynecology and Obstetrics (FIGO) stage I (p= 0.045), while the presence of microinvasion did not correlate with Claudin-1 expression. In contrast, we detected a highly significant association of Claudin-1 expression with the presence of peritoneal implants (p=0.003) and micropapillary pattern (p=0.047), which are features exclusively seen in serous BOT. Moreover, when we restricted our analysis to the subtype of serous BOT, the association of Claudin-1 expression with peritoneal implants (p<0.001) and micropapillary pattern (p =0.003) remained highly significant.ConclusionsIn conclusion, Claudin-1 expression is associated with the presence of peritoneal implants and micropapillary pattern, which have been shown to be associated with poor prognosis. We speculate that overexpression of Claudin-1 might be linked to the mitogen-activated protein kinase pathway activation in BOT and suggest further studies to define its prognostic and potential therapeutic value.

scholarly journals Overexpression of RASAL1 indicates poor prognosis and promotes invasion of ovarian cancer

2019 ◽  
Vol 14 (1) ◽  
pp. 133-140
Author(s):  
Rui-Xia Chang ◽  
Ai-Ling Cui ◽  
Lu Dong ◽  
Su-Ping Guan ◽  
Ling-Yan Jiang ◽  
...  
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
In Vitro Assays ◽  
Ovarian Adenocarcinoma ◽  
Invasion And Migration ◽  
Kaplan Meier ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
And Migration

AbstractRAS protein activator like-1 (RASAL1) exists in numerous human tissues and has been commonly demonstrated to act as a tumor suppressor in several cancers. This study aimed to identify the functional characteristics of RASAL1 in ovarian adenocarcinoma and a potential mechanism of action. We analyzed RASAL1 gene expression in ovarian adenocarcinoma samples and normal samples gained from the GEO and Oncomine databases respectively. Then the relationship between RASAL1 expression and overall survival (OS) was assessed using the Kaplan-Meier method. Furthermore, the biological effect of RASAL1 in ovarian adenocarcinoma cell lines was assessed by Quantitative real time-PCR (qRT-PCR), Cell Counting Kit-8 (CCK-8), western blot, wound healing and transwell assay. The statistical analysis showed patients with higher RASAL1 expression correlated with worse OS. The in vitro assays suggested knockdown of RASAL1 could inhibit cell proliferation, cell invasion and migration of ovarian adenocarcinoma. Moreover, the key proteins in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling pathway were also decreased in ovarian adenocarcinoma cells with RASAL1 silencing. These findings provide promising evidence that RASAL1 may be not only a powerful biomarker but also an effective therapeutic target of ovarian adenocarcinoma.

scholarly journals Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells

2019 ◽  
Vol 47 (3) ◽  
pp. 1288-1297 ◽  
Author(s):  
Zhanrong Qiang ◽  
Lingyu Meng ◽  
Caixia Yi ◽  
Lianying Yu ◽  
Wenxia Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Akt Pathway ◽  
High Dose ◽  
Human Gastric Cancer ◽  
Dependent Manner ◽  
Tensin Homolog ◽  
Phosphorylated Akt ◽  
Mitogen Activated Protein

Objective PD98059 is a potent and selective inhibitor of mitogen-activated protein kinase. Substantial preclinical evidence has shown an anti-tumor effect of curcumin on various solid tumors. This study aimed to investigate whether curcumin synergistically acts with PD98059 in exerting anti-gastric cancer effects. Methods The cell counting kit-8 assay was used to detect cell proliferation of the human gastric cancer MGC-803 cell line. Flow cytometry was performed to detect apoptosis. Western blotting was used to detect phosphatase and tensin homolog (PTEN) and phosphorylated Akt (p-Akt) expression levels. Quantitative reverse transcription-polymerase chain reaction was used to determine microRNA-21 (miR-21). Results A dose of 5 to 40 µM curcumin inhibited proliferation of MGC-803 cells in a dose- and time-dependent manner. A high dose of curcumin strongly inhibited p-Akt protein expression. With increasing curcumin levels, PTEN expression increased and miR-21 levels decreased. These results suggest that curcumin negatively modulated the miR-21/PTEN/Akt pathway. Moreover, after pretreatment with PD98059, cell apoptosis induced by curcumin was significantly increased. Additionally, the inhibitory effects of curcumin on the miR-21/PTEN/Akt pathway were significantly enhanced. Conclusion PD98059 combined with curcumin may be a potential strategy for managing gastric cancer.

scholarly journals The Ste20 Kinase Misshapen Regulates Both Photoreceptor Axon Targeting and Dorsal Closure, Acting Downstream of Distinct Signals

2000 ◽  
Vol 20 (13) ◽  
pp. 4736-4744 ◽  
Author(s):  
Yi-Chi Su ◽  
Corinne Maurel-Zaffran ◽  
Jessica E. Treisman ◽  
Edward Y. Skolnik
Keyword(s):  
Function Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Dorsal Closure ◽  
Axon Pathfinding ◽  
Sh3 Domains ◽  
Axon Targeting ◽  
Signaling Systems ◽  
Upstream Regulator ◽  
Mitogen Activated Protein

ABSTRACT We have previously shown that the Ste20 kinase encoded bymisshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module inDrosophila. msn is required to activate theDrosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), theDrosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect inmsn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue thedock mutant phenotype. Mosaic analysis reveals thatmsn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct upstream signaling systems.

scholarly journals Myoinvasive Pattern as a Prognostic Marker in Low-Grade, Early-Stage Endometrioid Endometrial Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1845 ◽  
Author(s):  
Ignacio Ruz-Caracuel ◽  
Jorge L Ramón-Patino ◽  
Álvaro López-Janeiro ◽  
Laura Yébenes ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Microsatellite Instability ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Low Grade ◽  
Gynecology And Obstetrics ◽  
Endometrioid Endometrial Carcinoma ◽  
Endometrial Carcinomas

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented –MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma.

scholarly journals Medical Significance of Uterine Corpus Endometrial Carcinoma Patients Infected With SARS-CoV-2 and Pharmacological Characteristics of Plumbagin

2021 ◽  
Vol 12 ◽  
Author(s):  
Yongming Li ◽  
Songzuo Yu ◽  
Yu Li ◽  
Xiao Liang ◽  
Min Su ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Endometrial Carcinoma ◽  
In Silico ◽  
Prognostic Index ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Molecular Pathways ◽  
Uterine Corpus ◽  
Mitogen Activated Protein ◽  
Pharmacologically Active

BackgroundClinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis.MethodsThe clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB.ResultsThe bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU).ConclusionsBased on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

scholarly journals Changes in Methylation across Structural and MicroRNA Genes Relevant for Progression and Metastasis in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5951
Author(s):  
Nitin Patil ◽  
Mohammed L. Abba ◽  
Chan Zhou ◽  
Shujian Chang ◽  
Timo Gaiser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cpg Islands ◽  
Enrichment Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Enrichment Analysis ◽  
Protein Coding ◽  
Normal Tissues ◽  
Mitogen Activated Protein ◽  
Microrna Genes

MiRs are important players in cancer and primarily genetic/transcriptional means of regulating their gene expression are known. However, epigenetic changes modify gene expression significantly. Here, we evaluated genome-wide methylation changes focusing on miR genes from primary CRC and corresponding normal tissues. Differentially methylated CpGs spanning CpG islands, open seas, and north and south shore regions were evaluated, with the largest number of changes observed within open seas and islands. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed several of these miRs to act in important cancer-related pathways, including phosphatidylinositol 3-kinase (PI3K)–protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. We found 18 miR genes to be significantly differentially methylated, with MIR124-2, MIR124-3, MIR129-2, MIR137, MIR34B, MIR34C, MIR548G, MIR762, and MIR9-3 hypermethylated and MIR1204, MIR17, MIR17HG, MIR18A, MIR19A, MIR19B1, MIR20A, MIR548F5, and MIR548I4 hypomethylated in CRC tumor compared with normal tissue, most of these miRs having been shown to regulate steps of metastasis. Generally, methylation changes were distributed evenly across all chromosomes with predominance for chromosomes 1/2 and protein-coding genes. Interestingly, chromosomes abundantly affected by methylation changes globally were rarely affected by methylation changes within miR genes. Our findings support additional mechanisms of methylation changes affecting (miR) genes that orchestrate CRC progression and metastasis.

scholarly journals Autocrine stimulation of IGF1 in estrogen-induced growth of endometrial carcinoma cells: involvement of the mitogen-activated protein kinase pathway followed by up-regulation of cyclin D1 and cyclin E

2009 ◽  
Vol 16 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Hiroyasu Kashima ◽  
Tanri Shiozawa ◽  
Tsutomu Miyamoto ◽  
Akihisa Suzuki ◽  
Junko Uchikawa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cyclin D1 ◽  
Endometrial Carcinoma ◽  
Carcinoma Cells ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Ishikawa Cells ◽  
Autocrine Stimulation ◽  
Stimulation Of

To examine estrogen-induced growth mechanisms of endometrial carcinoma, we investigated the estrogen-induced activation of the mitogen-activated protein kinase (MAPK) pathway and cell cycle regulators. Estradiol (E2) treatment at concentrations of 10−8 M and 10−6 M to estrogen receptor (ER)-positive endometrial carcinoma Ishikawa cells for 24 h resulted in increased cell proliferation by 20% and 28% respectively. The E2-induced proliferation was associated with the activation of extracellular signal-regulated kinase (MAPK)3/1 and up-regulation of cyclin D1 and E, which were suppressed by the addition of an MAP2K inhibitor (U0126) or an ER antagonist (ICI 182 780). Then, our screening for estrogen-inducible growth factors identified that IGF1 was up-regulated remarkably by E2. Immunoprecipitation using conditioned medium of Ishikawa cells after E2 treatment confirmed the E2-induced secretion of IGF1 protein. Treatment with recombinant IGF1 stimulated cell proliferation in a dose-dependent fashion, in association with MAPK3/1 phosphorylation and up-regulation of cyclin D1 and E. These IGF1-induced responses were suppressed by treatment with MAP2K inhibitor or anti-IGF1 receptor antibody. Immunohistochemical staining confirmed the expression of activated MAPK3/1 in normal proliferative phase endometria and endometrial carcinomas, indicating the involvement of this pathway in actively proliferating endometrial tissues in vivo. These findings suggest that E2-induced proliferation of endometrial carcinoma cells is mediated by the MAPK3/1 pathway via autocrine stimulation of IGF1.

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