303 Hospital

Nanning, China

303 Hospital

Nanning, China
Time filter
Source Type

Su R.,Chinese Institute of Basic Medical Sciences | Lin H.-S.,Chinese Institute of Basic Medical Sciences | Zhang X.-H.,303 Hospital | Yin X.-L.,303 Hospital | And 12 more authors.
Oncogene | Year: 2015

MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy. © 2015 Macmillan Publishers Limited.

Gong J.-N.,Peking Union Medical College | Yu J.,Peking Union Medical College | Lin H.-S.,Peking Union Medical College | Zhang X.-H.,303 Hospital | And 9 more authors.
Cell Death and Differentiation | Year: 2014

Abnormal proliferation, apoptosis repression and differentiation blockage of hematopoietic stem/progenitor cells have been characterized to be the main reasons leading to acute myeloid leukemia (AML). Previous studies showed that miR-29a and miR-29b could function as tumor suppressors in leukemogenesis. However, a comprehensive investigation of the function and mechanism of miR-29 family in AML development and their potentiality in AML therapy still need to be elucidated. Herein, we reported that the family members, miR-29a, -29b and -29c, were commonly downregulated in peripheral blood mononuclear cells and bone marrow (BM) CD34+ cells derived from AML patients as compared with the healthy donors. Overexpression of each miR-29 member in THP1 and NB4 cells markedly inhibited cell proliferation and promoted cell apoptosis. AKT2 and CCND2 mRNAs were demonstrated to be targets of the miR-29 members, and the role of miR-29 family was attributed to the decrease of Akt2 and CCND2, two key signaling molecules. Significantly increased Akt2, CCND2 and c-Myc levels in the AML cases were detected, which were correlated with the decreased miR-29 expression in AML blasts. Furthermore, a feed-back loop comprising of c-Myc, miR-29 family and Akt2 were found in myeloid leukemogenesis. Reintroduction of each miR-29 member partially corrected abnormal cell proliferation and apoptosis repression and myeloid differentiation arrest in AML BM blasts. An intravenous injection of miR-29a, -29b and -29c in the AML model mice relieved leukemic symptoms significantly. Taken together, our finding revealed a pivotal role of miR-29 family in AML development and rescue of miR-29 family expression in AML patients could provide a new therapeutic strategy. © 2014 Macmillan Publishers Limited All rights reserved.

Wang X.-S.,Peking Union Medical College | Gong J.-N.,Peking Union Medical College | Yu J.,Peking Union Medical College | Wang F.,Peking Union Medical College | And 7 more authors.
Blood | Year: 2012

Although microRNAs (miRNAs) are increasingly linked to various physiologic processes, including hematopoiesis, their function in the myeloid development is poorly understood. We detected upregulation of miR-29a and miR-142-3p during myeloid differentiation in leukemia cell lines and CD34 + hematopoietic stem/ progenitor cells. By gain-of-function and loss-of-function experiments, we demonstrated that both miRNAs promote the phorbol 12-myristate 13-acetate-induced monocytic and all-trans-retinoic acid-induced granulocytic differentiation of HL- 60, THP-1, or NB4 cells. Both the miRNAs directly inhibited cyclin T2 gene, preventing the release of hypophosphorylated retinoblastoma and resulting in induction of monocytic differentiation. In addition, a target of miR-29a, cyclin-dependent kinase 6 gene, and a target of miR-142-3p, TGF-β-activated kinase 1/MAP3K7 binding protein 2 gene, are involved in the regulation of both monocytic and granulocytic differentiation. A significant decrease of miR-29a and 142-3p levels and an obvious increase in their target protein levels were also observed in blasts from acute myeloid leukemia. By lentivirus-mediated gene transfer, we demonstrated that enforced expression of either miR- 29a or miR-142-3p in hematopoietic stem/ progenitor cells from healthy controls and acute myeloid leukemia patients down-regulated expression of their targets and promoted myeloid differentiation. These findings confirm that miR-29a and miR-142-3p are key regulators of normal myeloid differentiation and their reduced expression is involved in acute myeloid leukemia development. © 2012 by The American Society of Hematology.

Peng J.,PLA Fourth Military Medical University | Li H.,303 Hospital | Miao D.,PLA Fourth Military Medical University | Feng X.,PLA Fourth Military Medical University | Xiao W.,PLA Fourth Military Medical University
Iranian Red Crescent Medical Journal | Year: 2013

Background: Considerable reports concerned the framing effect in medical situations. But quite few of them noticed to explore the differences among the various kinds of framing effects.Objective: In the present study, five different types of framing effects were examined and the effect sizes of them were compared.Materials and Methods: Medical decision making problems concerning medicine effect evaluation, patient's compliance, treatment and doctor options selection were established. All the problems were described in both positive and negative frames. 500 undergraduates as participants were randomly divided into ten groups. Participants from each group were asked to finish one decision making task. Results: All the frames examined leaded to significant framing effects: When the Asia Disease Problem was described in a positive frame, participants preferred the conservative frame than the risky one, while if in a negative frame, the preference reversed (P < 0.01). If the drug effect was described as "of 100 patients taking this kind of medicine, 70 patients became better", people tended to make more positive evaluations, compared with described as "of 100 patients taking this kind of medicine, 30 patients didn't become better" (P < 0.01). Doctors' advices were respectively described in a baneful or beneficial frame and the former one resulted in a better compliance (P < 0.05). If treatment options were described with a survival rate, people tended to choose risky option, while if described with a mortality rate, people tended to choose conservative option (P < 0.05). The number sized framing effect was also tested to be significant (P < 0.01). The five types of framing effects were small to big in effect size. Conclusions: Medical decision making can be affected by frame descriptions. Attentions should be paid on the standardization of description in medical practice.

Loading 303 Hospital collaborators
Loading 303 Hospital collaborators