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1.
Oncol Res ; 28(4): 345-355, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32138807

ABSTRACT

Anaplastic thyroid carcinoma (ATC) is resistant to standard therapies and has no effective treatment. Eukaryotic translation initiation factor 5A2 (EIF5A2) has shown to be upregulated in many malignant tumors and proposed to be a critical gene involved in tumor metastasis. In this study, we aimed to investigate the expression status of EIF5A2 in human ATC tissues and to study the role and mechanisms of EIF5A2 in ATC tumorigenesis in vitro and in vivo. Expression of EIF5A2 protein was analyzed in paraffin-embedded human ATC tissues and adjacent nontumorous tissues (ANCT) (n=24) by immunochemistry. Expressions of EIF5A2 mRNA and protein were analyzed in fresh-matched ATC and ANCT (n=23) and ATC cell lines by real-time polymerase chain reaction (PCR) and Western blotting. The effect of targeting EIF5A2 with short hairpin RNA (shRNA) or EIF5A2 overexpression on the ATC tumorigenesis and TGF-/Smad2/3 signals in vitro and in vivo was investigated. Expression of EIF5A2 was significantly upregulated in ATC tissues and cell lines compared with ANCT and normal follicular epithelial cell line. Functional studies found that targeting EIF5A2 induced SW1736 cell death in vitro and in vivo, followed by significantly downregulated phosphorylation of Smad2/3 (p-Smad2/3) in SW1736 cells at the protein level. Ectopic expression of EIF5A2 could promote 8505C cell growth in vitro and in vivo, followed by significantly upregulated p-Smad3 at the protein level. Recombinant human TGF-1 (hTGF-1) treatment decreased the antiproliferative activity of the EIF5A2 downexpressing 8505C cells through reversing pSmad2/3. Using the specific inhibitor SB431542 to block TGF- pathway or Smad3 siRNA to knock down Smad3 increased the antiproliferative activity of the EIF5A2-overexpressing 8505C cells through inhibiting pSmad2/3. Our findings indicated that EIF5A2 controled cell growth in ATC cells, and EIF5A/TGF-/Smad2/3 signal may be a potential therapeutic target for ATC treatment.


Subject(s)
Peptide Initiation Factors/metabolism , RNA-Binding Proteins/metabolism , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Neoplasms/metabolism , Transforming Growth Factor beta/metabolism , Apoptosis , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Humans , Peptide Initiation Factors/genetics , RNA, Messenger/genetics , RNA, Small Interfering/genetics , RNA-Binding Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/genetics , Up-Regulation , Eukaryotic Translation Initiation Factor 5A
2.
Bioengineered ; 11(1): 189-200, 2020 12.
Article in English | MEDLINE | ID: mdl-32050841

ABSTRACT

MicroRNAs (miRNAs) have emerged as critical regulators of neuronal survival during cerebral ischemia/reperfusion injury. Accumulating evidence has shown that miR-211 plays a crucial role in regulating apoptosis and survival in various cell types. However, whether miR-211 is involved in regulating neuronal survival during cerebral ischemia/reperfusion injury remains unknown. In this study, we aimed to explore the biological role of miR-211 in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and transient cerebral ischemia/reperfusion (I/R) injury in vitro and in vivo. We found that miR-211 expression was significantly downregulated in PC12 cells in response to OGD/R and in the penumbra of mouse in response to MCAO. Overexpression of miR-211 alleviated OGD/R-induced PC12 cell apoptosis, whereas miR-211 inhibition facilitated OGD/R-induced PC12 cell apoptosis in vitro. Moreover, overexpression of miR-211 reduced infarct volumes, neurologic score, and neuronal apoptosis in vivo, whereas miR-211 inhibition increased infarct volumes, neurologic score and neuronal apoptosis in vivo. Notably, our results identified P53-up-regulated modulator of apoptosis (PUMA) as a target gene of miR-211. Our findings suggested that miR-211 may protect against MCAO injury by targeting PUMA in rats, which paves a potential new way for the therapy of cerebral I/R injury.


Subject(s)
MicroRNAs/metabolism , Reperfusion Injury/metabolism , Reperfusion Injury/therapy , Animals , Apoptosis/genetics , Apoptosis/physiology , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Blotting, Western , Brain/metabolism , Flow Cytometry , In Situ Nick-End Labeling , Male , Mice, Inbred C57BL , MicroRNAs/genetics , Neurons/metabolism , PC12 Cells , Rats , Reperfusion Injury/genetics
3.
Bioengineered ; 10(1): 383-389, 2019 12.
Article in English | MEDLINE | ID: mdl-31791180

ABSTRACT

Downregulation of lncRNA H19 (H19) expression is associated with an unfavorable prognosis in some cancers. However, little was known as to whether there was an association between H19 and minimally invasive follicular thyroid carcinoma (MI-FTC). In our study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine H19 expression in 186 patients with MI-FTC who underwent initial surgery. Of the 186 patients with MI-FTC, 21 patients show distant metastasis (M+)at the initial operation established the diagnosis of MI-FTC. Of the 165 patients who did not show distant metastasis at diagnosis during the follow-up period (≥10 years), 28 patients undergone M+ and 137 patients has no distant metastasis(M-)after the initial operation. Low H19 expression was associated with large tumor size, vascular invasion, and distant metastasis. Univariate analysis showed that gender (male), age (45 years or older), primary tumor size (4 cm or more), vascular invasion and H19 level (<1.12) were significant prognostic factors related to postoperative distant metastases. Multivariate analysis showed that age, primary tumor size (4 cm or more) and vascular invasion was a significant prognostic factor for survival. Patients with low H19 expression showed a poorer outcome in MI-FTC patients. Receiver-operating characteristic (ROC) curve analysis demonstrated H19 could distinguish M+ from M- patientswith a value of area under the curve (AUC). Our findings suggest that H19 is a potential prognostic factor for evaluating prognosis and the metastatic potential of MI-FTC at an initial operation stage.


Subject(s)
Adenocarcinoma, Follicular/diagnosis , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/genetics , Thyroid Neoplasms/diagnosis , Adenocarcinoma, Follicular/genetics , Adenocarcinoma, Follicular/mortality , Adenocarcinoma, Follicular/surgery , Adult , Aged , Area Under Curve , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Prognosis , RNA, Long Noncoding/blood , ROC Curve , Retrospective Studies , Sex Factors , Survival Analysis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/mortality , Thyroid Neoplasms/surgery , Tumor Burden
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