scholarly journals miR-139-5p Regulates the Proliferation of Acute Promyelocytic Leukemia Cells by Targeting MNT

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yueyue Fu ◽  
Limin Li ◽  
Jinxiao Hou ◽  
Huibo Li ◽  
Chengfang Lv ◽  
...  

Acute promyelocytic leukemia (APL) patients with progressive leukocytosis are more likely to have various complications and poor outcomes. However, the regulatory roles of microRNAs in the leukocytosis of APL have not been clarified. Our study aims to evaluate the effects of miRNAs on leukocytosis during induction therapy of APL patients and explore its potential mechanisms. During induction treatment, patients with white blood cell count higher than 10 × 109/L were divided into leukocytosis group and others were nonleukocytosis group. Using microarray assays, we found that miR-139-5p was significantly downregulated in the leukocytosis group. Elevated expression of miR-139-5p inhibited the proliferation of NB4 cells by arresting the cell cycle and inducing apoptosis. We further identified that MNT was a target of miR-139-5p. miR-139-5p significantly inhibited the proliferation, invasion, and migration function of NB4 cells through targeting MNT. Strategies for regulating miR-139-5p or MNT expression might provide new therapeutic approaches for progressive leukocytosis in APL.

2020 ◽  
Author(s):  
Peihong Shao ◽  
Chengshi Wei ◽  
Yun Wang

Abstract Background: In this study, we planned to investigate the function and potential mechanisms of Alpha-1,3-mannosyltransferase (ALG3) in oral squamous cell carcinoma (OSCC). Methods: Data from The Cancer Genome Atlas (TCGA) was used to analyze ALG3 expression and its effect on the prognosis of patients with OSCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was applied to explore the signaling pathways related to ALG3. In OSCC cells, ALG3 expression was measured by qPCR and western blot. Cell counting kit-8, colony formation, and transwell assays were implemented to detect the effects of ALG3 on the malignant biological properties OSCC cells. The expression of key proteins related to CDK-Cyclin pathway was detected by western blot. Results: The expression of ALG3 in OSCC samples was higher than that of the control samples, and the increase of ALG3 expression was related to unfavorable prognosis of OSCC patients. Additionally, the elevated expression of ALG3 was associated with pathological stage, lymph node metastasis and primary lesion in OSCC patients. ALG3 depletion blocked the growth, colony formation, invasion and migration of OSCC cells, while over-expression ALG3 reversed these phenomena. Moreover, exhaustion of ALG3 resulted in decreased expression of MCM7, CCNB2, CDK1 and PCNA, while these phenomena were inversed after ALG3 up-regulation. Conclusions: The enhancement of ALG3 expression promoted the aggressive biological behaviors of OSCC cells probably by promoting CDK-Cyclin pathway.


2005 ◽  
Vol 7 (4) ◽  
pp. 633-641 ◽  
Author(s):  
Yu Cao ◽  
Fang Wang ◽  
Hong-Yan Liu ◽  
Zhao-Di Fu ◽  
Rui Han

2016 ◽  
Vol 136 (4) ◽  
pp. 210-218 ◽  
Author(s):  
Muhamed Baljevic ◽  
Bogdan Dumitriu ◽  
Ju-Whei Lee ◽  
Elisabeth M. Paietta ◽  
Peter H. Wiernik ◽  
...  

Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established. We report the results for a large cohort of 187 PML/RARα-positive APL patients. No germline mutations in the TERT or TERC genes were identified. Codon 279 and 1062 TERT polymorphisms were present at a frequency similar to that in the general population. TL measured in blood or marrow mononuclear cells at diagnosis was significantly shorter in the APL patients than in healthy volunteers, and shorter telomeres at diagnosis were significantly associated with high-risk disease. For patients who achieved complete remission, the median increase in TL from diagnosis to remission (delta TL) was 2.0 kilobase (kb), and we found delta TL to be the most powerful predictor of overall survival when compared with well-established risk factors for poor outcomes in APL.


2015 ◽  
Vol 747 ◽  
pp. 36-44 ◽  
Author(s):  
Sook-Kyoung Heo ◽  
Eui-Kyu Noh ◽  
Dong-Joon Yoon ◽  
Jae-Cheol Jo ◽  
SuJin Koh ◽  
...  

2002 ◽  
Vol 277 (51) ◽  
pp. 49504-49510 ◽  
Author(s):  
Ji Li ◽  
Peili Chen ◽  
Natasha Sinogeeva ◽  
Myriam Gorospe ◽  
Robert P. Wersto ◽  
...  

Arsenic trioxide (As2O3) is highly effective for the treatment of acute promyelocytic leukemia, even in patients who are unresponsive to all-trans-retinoic acid therapy. As2O3is believed to function primarily by promoting apoptosis, but the underlying molecular mechanisms remain largely unknown. In this report, using cDNA arrays, we have examined the changes in gene expression profiles triggered by clinically achievable doses of As2O3in acute promyelocytic leukemia NB4 cells.CASPASE-10expression was found to be potently induced by As2O3. Accordingly, caspase-10 activity also substantially increased in response to As2O3treatment. A selective inhibitor of caspase-10, Z-AEVD-FMK, effectively blocked caspase-3 activation and significantly attenuated As2O3-triggered apoptosis. Interestingly, the treatment of NB4 cells with As2O3markedly increased histone H3 phosphorylation at serine 10, an event that is associated with acetylation of the lysine 14 residue. Chromatin immunoprecipitation assays revealed that As2O3potently enhances histone H3 phosphoacetylation at theCASPASE-10locus. These results suggest that the effect of As2O3on histone H3 phosphoacetylation at theCASPASE-10gene may play an important role in the induction of apoptosis and thus contribute to its therapeutic effects on acute promyelocytic leukemia.


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