miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells.
نویسندگان
چکیده
Glioblastomas rely mainly on aerobic glycolysis to sustain proliferation and growth; however, little is known about the regulatory mechanisms of metabolism in glioblastoma stem cells. We show that miR-143 is significantly down-regulated in glioma tissues and glioblastoma stem-like cells (GSLCs), while miR-143 over-expression inhibits glycolysis by directly targeting hexokinase 2, and promotes differentiation of GSLCs. Moreover, miR-143 inhibits proliferation of GSLCs under hypoxic conditions and decreases tumor formation capacity of GSLCs in vivo. We also show that a combination of miR-143 and 2-DG, a widely used glycolysis inhibitor, has synergistic effects against GSLCs. miR-143 is a potential therapeutic target for glioblastoma treatment.
منابع مشابه
miR-143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma.
Despite evidence that the crucial role of NUAK family, SNF1-like kinase, 2 [NUAK2; also known as sucrose non-fermenting 1 (SNF1)-like kinase (SNARK)], has been highlighted in cancer development and in tumor progression, to the best of our knowledge, there are no studies available to date on the role of NUAK2 in glioblastoma. Thus, in this study, in order to determine the role of NUAK2 in gliobl...
متن کاملActive glycolytic metabolism in CD133(+) hepatocellular cancer stem cells: regulation by MIR-122
Although altered metabolic pathway is an important diagnostic maker and therapeutic target in cancer, it is poorly understood in cancer stem cells (CSCs). Here we show that the CD133 (+) hepatocellular CSCs have distinct metabolic properties, characterized by more active glycolysis over oxidative phosphorylation, compared to the CD133 (-) cells. Inhibition of PDK4 and LDHA markedly suppresses C...
متن کاملmiR-29b attenuates tumorigenicity and stemness maintenance in human glioblastoma multiforme by directly targeting BCL2L2
Glioblastoma multiforme (GBM) is the most common malignant brain tumor and exhibits aggressive and invasive behavior. We previously identified four miRNAs-miR-29b, 494, 193a-3p, and 30e-with enhanced expression in GBM following treatment of ionizing radiation by miRNA microarray analysis. In this study, we found that only miR-29b inhibited tumor cell migration and invasion by reducing MMP-2 act...
متن کاملMetabolic alterations in highly tumorigenic glioblastoma cells: preference for hypoxia and high dependency on glycolysis.
Recent studies suggest that a small subpopulation of malignant cells with stem-like properties is resistant to chemotherapy and may be responsible for the existence of residual cancer after treatment. We have isolated highly tumorigenic cancer cells with 100-fold increase in tumor initiating capacity from the tumor xenografts of human glioblastoma U87 cells in mice. These cells exhibit stem-lik...
متن کاملMicroRNA-7 inhibits the stemness of prostate cancer stem-like cells and tumorigenesis by repressing KLF4/PI3K/Akt/p21 pathway.
Up to now, the molecular mechanisms underlying the stemness of prostate cancer stem cells (PCSCs) are still poorly understood. In this study, we demonstrated that microRNA-7 (miR-7) appears to be a novel tumor-suppressor miRNA, which abrogates the stemness of PCSCs and inhibits prostate tumorigenesis by suppressing a key stemness factor KLF4. MicroRNA-7 is down-regulated in prostate cancer cell...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer letters
دوره 333 2 شماره
صفحات -
تاریخ انتشار 2013