目的探索转录因子EB（TFEB）及其靶基因在硼替佐米治疗多发性骨髓瘤（MM）中的作用及分子机制。方法通过GTRD网站（http://gtrd.biouml.org/）预测TFEB靶基因，筛选出Ptch1基因。实时荧光定量PCR和Western blot法检测硼替佐米作用于MM细胞系RPMI8226和U266后Ptch1的表达变化。siRNA-TFEB分别转染RPMI8226和U266细胞系，实时荧光定量PCR和Western blot法检测Ptch1/Hedgehog信号通路关键因子（Ptch1、Gli1）的mRNA和蛋白相对表达情况。在MM细胞系中用慢病毒转染过表达Ptch1，吖啶橙染色观察自噬现象，Western blot法检测各组细胞自噬相关因子（LC3B、Beclin-1、Lamp-1）蛋白相对表达量，溶酶体荧光探针观察溶酶体数量变化。结果硼替佐米（6.0×10−6 mmol/L）处理RPMI8226和U266细胞系24 h，硼替佐米组Ptch1的mRNA和蛋白的相对表达水平均较空白对照组降低（P值均<0.05），转染siRNA-TFEB后逆转了硼替佐米对Hedgehog通路中关键因子Ptch1、Gli的抑制作用。Ptch1过表达显著减少了经硼替佐米处理的RPMI8226和U266细胞系中自噬相关因子LC3B、Beclin1、Lamp1蛋白的相对表达量（P值均为0.001）。吖啶橙染色显示两种细胞系酸性囊泡数量均减少（P值均为0.001），反映溶酶体数量的溶酶体探针相对荧光表达亦减少（RPMI8226和U266细胞系的P值分别为0.001、0.007）。结论敲低TFEB可靶向促进Ptch1/Hedgehog信号通路表达而减少硼替佐米诱导的MM细胞自噬，并逆转硼替佐米对MM细胞系的增殖抑制作用。
3Chimeric Antigen Receptor T Cells Targeting LILRB4, an Immunoreceptor Mediating T-Cell Suppression, Are Potently Effective in Multiple Myeloma
Chimeric Antigen Receptor T Cells Targeting LILRB4, an Immunoreceptor Mediating T-Cell Suppression, Are Potently Effective in Multiple Myeloma
Read moreOncolytic Reovirus Sensitizes Multiple Myeloma Cells to Anti-PD-L1 Therapy
Oncolytic Reovirus Sensitizes Multiple Myeloma Cells to Anti-PD-L1 Therapy
Anti-Myeloma Effects of Panobinostat in Combination with Duvelisib
Anti-Myeloma Effects of Panobinostat in Combination with Duvelisib
1Blocking Pleiotrophin Activity Inhibits Multiple Myeloma (MM) Cell Growth In Vitro and in a Severe Combined Immunodeficient (SCID)-hu Murine Model of Human MM.
Blocking Pleiotrophin Activity Inhibits Multiple Myeloma (MM) Cell Growth In Vitro and in a Severe Combined Immunodeficient (SCID)-hu Murine Model of Human MM.
Read more6A New Class of T-Cell Bispecific Antibodies for the Treatment of Multiple Myeloma, Binding to B Cell Maturation Antigen and CD3 and Showing Potent, Specific Antitumor Activity in Myeloma Cells and Long Duration of Action in Cynomolgus Monkeys
A New Class of T-Cell Bispecific Antibodies for the Treatment of Multiple Myeloma, Binding to B Cell Maturation Antigen and CD3 and Showing Potent, Specific Antitumor Activity in Myeloma Cells and Long Duration of Action in Cynomolgus Monkeys
Read moreDifferential Effects of Hsp70 Inhibition within the Tumor and Microenvironment in Multiple Myeloma.
Differential Effects of Hsp70 Inhibition within the Tumor and Microenvironment in Multiple Myeloma.
2HIF-1 Supports the Survival of Multiple Myeloma Cells through the Induction of Survivin Gene.
HIF-1 Supports the Survival of Multiple Myeloma Cells through the Induction of Survivin Gene.
82Novel therapies for multiple myeloma.
Novel therapies for multiple myeloma.
10PARP Inhibition Synergizes with Melphalan but Does not Reverse Resistance Completely.
PARP Inhibition Synergizes with Melphalan but Does not Reverse Resistance Completely.
4MiR‑1343‑3p inhibits autophagy by directly targeting ATG7 in multiple myeloma cells
Multiple myeloma (MM) is the second most common type of hematological malignancy globally. Despite application of several new drugs, such as daratumumab, bortezomib/lenalidomide/dexamethasone, in combination with hematopoietic stem cell transplantation, overall prognosis remains poor and the pathological mechanism of MM is still unknown. The present study used TargetScan to predict autophagy-related 7 (ATG7) as a candidate target gene of microRNA (miR)-1343-3p and confirmed the interaction between miR-1343-3p and the ATG7 3' untranslated region (3'UTR) using a dual-luciferase reporter assay. In U266 and RPMI-8226 MM cell lines, miR-1343-3p mimic transfection decreased mRNA and protein levels of ATG7, while miR-1343-3p inhibition increased ATG7 expression levels using reverse transcription-qPCR and western blot analysis. miR-1343-3p mimic transfection inhibited U266 and RPMI-8226 cell survival. Finally, miR-1343-3p regulated ATG7 and autophagy in MM cells using western blot analysis. The present findings suggested that miR-1343-3p may regulate ATG7 and autophagy by directly targeting the 3'UTR of ATG7. To the best of our knowledge, there are no direct data showing the roles of miR-1343-3p in development of MM; however, miR-1343-3p may be considered a potential target for MM treatment.
Read more4IMiDs® Immunomodulatory Agents Regulate Interferon-Stimulated Genes through Cereblon-Mediated Aiolos Destruction in Multiple Myeloma (MM) Cells: Identification of a Novel Mechanism of Action and Pathway for Resistance
IMiDs® Immunomodulatory Agents Regulate Interferon-Stimulated Genes through Cereblon-Mediated Aiolos Destruction in Multiple Myeloma (MM) Cells: Identification of a Novel Mechanism of Action and Pathway for Resistance
Read moreInhibition of Multiple Myeloma Cell Adhesion to Fibronectin by Ephrin Ligation.
Inhibition of Multiple Myeloma Cell Adhesion to Fibronectin by Ephrin Ligation.
13Interleukin-6 Drives Multiple Myeloma Progression By up-Regulating of CD147/Emmprin Expression
Interleukin-6 Drives Multiple Myeloma Progression By up-Regulating of CD147/Emmprin Expression
29Knockdown of NUPR1 inhibits the growth of U266 and RPMI8226 multiple myeloma cell lines via activating PTEN and caspase activation‑dependent apoptosis.
Nuclear protein‑1 (NUPR1) is a stress response factor that is important in the development of several human malignant tumor cells. However, the role of NUPR1 in multiple myeloma (MM) remains to be fully elucidated. In the present study, it was found that the mRNA levels of NUPR1 were significantly higher in specimens from patients with MM and MM cell lines (U266 and RPMI8226) than in cells of normal human bone marrow. The present study was undertaken to investigate the function of NUPR1 in the growth and apoptosis of MM cell lines. A lentivirus‑mediated short hairpin RNA was used to specifically inhibit the mRNA and protein expression of NUPR1 in the U266 and RPMI8226MM cell lines. Flow cytometry and Cell Counting Kit‑8 assays were applied to examine the apoptosis and proliferation of U266 and RPMI8226 cell lines. The results revealed the inhibitory effect of NUPR1 silencing on the proliferation of U266 and RPMI8226 cells through inducing apoptosis, and arrest of cell cycle at the G0/G1phase. Furthermore, NUPR1 silencing caused activation of caspase‑3,‑8 and‑9 and influenced specific gene expression, including an increase of phosphatase and tensin homolog (PTEN) and decrease of B‑cell lymphoma 2 and proliferating cell nuclear antigen. These findings showed that NUPR1 may be involved in the proliferation and apoptosis of MM cells by adjusting caspase proteins and PTEN, suggesting that NUPR1 may be a novel therapeutic target for MM.
Read more9Sprouty2 regulates proliferation and survival of multiple myeloma byinhibiting activation of the ERK1/2 pathway invitro and invivo.
Sprouty2 regulates proliferation and survival of multiple myeloma byinhibiting activation of the ERK1/2 pathway invitro and invivo.
Read more
Copyright 2026 Cactus Communications. All rights reserved.
