Analytical Cellular Pathology
·
2023
·
IF 3.2
Fan Du,Ting Jin,Li Wang
Objective. Acute myeloid leukemia (AML) is a heterogeneous malignancy with a low long-term survival rate. The aim of this study was to investigate the effects of decitabine (DAC) treatment cell proliferation and apoptosis in AML and role of the expression of LINC00599 and, consequently, miR-135a-5p. Materials and Methods. Human promyelocytic leukemia cells (HL-60) and human acute lymphatic leukemia (CCRF-CEM) cells were treated with various concentrations of DAC. Cell proliferation in each group was detected using the cell counting kit 8. For each group, apoptosis and reactive oxygen species (ROS) levels were detected using flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) was performed to examine the expression of lncRNA LINC00599. The expression of apoptosis-related proteins was analyzed using western blotting. The regulatory relationship between miR-135a-5p and LINC00599 was verified by constructing miR-135a-5p mimics, miR-135a-5p inhibit, wild type LINC00599 3-untranslated region (UTR), and mutant LINC00599 3-UTR. Ki-67 expression in the tumor tissues of nude mice was detected using immunofluorescent assays. Results. Both DAC and LINC00599 Inhibit groups were able to significantly reduce the proliferation of HL60 and CCRF-CEM cells, increase apoptosis, upregulate the expression of Bad, cleaved caspase-3, and miR-135a-5p, downregulate the expression of Bcl-2, and elevate ROS levels in cells, with these effects being more pronounced after combined treatment with DAC and LINC00599 Inhibit. In comparison to mimic NC, the miR-135a-5p mimic group significantly decreased the relative fluorescence activity ratio of LINC00599 3-UTR wild-type CCRF-CEM cells. The LINC00599 Inhibit and miR-135a-5p mimic groups exhibited substantially reduced proliferation of HL60 and CCRF-CEM cells, increased apoptosis, upregulated Bad, cleaved caspase-3, and miR-135a-5p expression, along with downregulated Bcl-2 and LINC00599 expression and increased ROS levels in cells; these effects were more pronounced after LINC00599 Inhibit was combined with miR-135a-5p mimics. In vivo experiments revealed that both DAC and LINC00599 Inhibit were able to considerably reduce the long diameter, short meridian, volume, and mass of tumors, increase miR-135a-5p expression, and decrease LINC00599 and ki-67 expression in tumor tissues of nude mice. This effect was more pronounced when the DAC and LINC00599 Inhibit were used in combination. Conclusion. DAC regulates the expression of miR-135a-5p by regulating the expression of LINC00599, which in turn affects cell proliferation, apoptosis, and tumor proliferation. Our findings provide a theoretical basis for improving the clinical outcome of AML.
研究领域:
肿瘤学
·
血液学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Science
·
2020
·Vol. 11
·期 7
·1948-1956
·
IF 9.346
Qianying Zhang,Wenjing Wang,Shan Huang,Sha Yu,Tingting Tan,Jian-Rong Zhang,Jun-Jie Zhu
The effective capture, release and reanalysis of circulating tumor cells (CTCs) are of great significance to acquire tumor information and promote the progress of tumor therapy. Particularly, the selective release of multiple types of CTCs is critical to further study; however, it is still a great challenge. To meet this challenge, we designed a smart DNAzyme probe-based platform. By combining multiple targeting aptamers and multiple metal ion responsive DNAzymes, efficient capture and selective release of multiple types CTCs were realized. Sgc8c aptamer integrated Cu2+-dependent DNAzyme and TD05 aptamer integrated Mg2+-dependent DNAzyme can capture CCRF-CEM cells and Ramos cells respectively on the substrate. With the addition of Cu2+ or Mg2+, CCRF-CEM cells or Ramos cells will be released from the substrate with specific selectivity. Furthermore, our platform has been successfully demonstrated in the whole blood sample. Therefore, our capture/release platform will benefit research on the molecular analysis of CTCs after release and has great potential for cancer diagnosis and individualized treatment.
研究领域:
生物技术
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Materials Advances
·
2022
·Vol. 3
·期 18
·7080-7086
·
IF 0
Xueke Wu,Chenyuan Yan,Lixuan Mu,Yuan Wang,Guangwei She,Wensheng Shi
By assembling fluorophore-marked DNA stem-loops on the surface of gold nanobipyramids (AuNBPs) with an efficient photothermal conversion, we fabricated a multifunctional photothermal reagent (AuNBPs-mPEG/AA-TR). The sgc8 sequences that were embedded inside the DNA stem-loops can specifically target the PTK7, an overexpressed protein located on the surface of CCRF-CEM cells (human acute lymphoblastic leukemia T lymphocyte) to realize an active targeting function. Before the AuNBPs-mPEG/AA-TR bind to the PTK7 proteins, the DNA stem-loops are folded, and the fluorophore linked on the DNA stem-loop will be close to the AuNBPs. In this configuration, the fluorescence from the fluorophore is quenched by the AuNBPs. However, when the AuNBPs-mPEG/AA-TR bound to the PTK7 proteins through the sgc8 sequences, the DNA stem-loops can be opened partially to enable the fluorophore to be far away from the AuNBPs. As a result, the fluorescent signal will be activated. Therefore, the fluorescence can be used as a visual signal to reveal the binding between the AuNBPs-mPEG/AA-TR and CCRF-CEM cells (usually called activatable fluorescence labelling). While under irradiation of an 808 nm laser, the CCRF-CEM cells could be ablated through the photothermal therapy of the AuNBPs-mPEG/AA-TR with a high photothermal efficiency. Applying the AuNBPs-mPEG/AA-TR to Human B lymphoma cells (Ramos cells) and CCRF-CEM cells, we found that only the CCRF-CEM cells can be effectively targeted, actively fluorescently labeled, and readily ablated by the AuNBPs-mPEG/AA-TR. This work provides an alternative photothermal agent for the targeted therapy of tumors.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
分子生物学
·
光学
✓ 已验证
DOI
危险品化学品经营许可证（带存储）