The m6A reader IGF2BP3 promotes acute myeloid leukemia progression by enhancing RCC2 stability
The m6A reader IGF2BP3 promotes acute myeloid leukemia progression by enhancing RCC2 stability
Zhang Nan(The Second Affiliated Hospital of Chongqing Medical University); Shen Yan(The Second Affiliated Hospital of Chongqing Medical University); Li Huan(The Second Affiliated Hospital of Chongqing Medical University); Chen Ying(The Second Affiliated Hospital of Chongqing Medical University); Zhang Ping(The Second Affiliated Hospital of Chongqing Medical University); Lou Shifeng(The Second Affiliated Hospital of Chongqing Medical University); Deng Jianchuan(The Second Affiliated Hospital of Chongqing Medical University)
54권, 1~12쪽
초록
N6-methyladenosine (m6A) is the most abundant posttranscriptional modification of mRNA in eukaryotes. Recent evidence suggests that dysregulated m6A-associated proteins and m6A modifications play a pivotal role in the initiation and progression of diseases such as cancer. Here, we identified that IGF2BP3 is specifically overexpressed in acute myeloid leukemia (AML), a subtype of leukemia associated with poor prognosis and high genetic risk. IGF2BP3 is required for maintaining AML cell survival in an m6A-dependent manner, and knockdown of IGF2BP3 dramatically suppresses the apoptosis, reduces the proliferation, and impairs the leukemic capacity of AML cells in vitro and in vivo. Mechanistically, IGF2BP3 interacts with RCC2 mRNA and stabilizes the expression of m6A-modified RNA. Thus, we provided compelling evidence demonstrating that the m6A reader IGF2BP3 contributes to tumorigenesis and poor prognosis in AML and can serve as a target for the development of cancer therapeutics.
Abstract
N6-methyladenosine (m6A) is the most abundant posttranscriptional modification of mRNA in eukaryotes. Recent evidence suggests that dysregulated m6A-associated proteins and m6A modifications play a pivotal role in the initiation and progression of diseases such as cancer. Here, we identified that IGF2BP3 is specifically overexpressed in acute myeloid leukemia (AML), a subtype of leukemia associated with poor prognosis and high genetic risk. IGF2BP3 is required for maintaining AML cell survival in an m6A-dependent manner, and knockdown of IGF2BP3 dramatically suppresses the apoptosis, reduces the proliferation, and impairs the leukemic capacity of AML cells in vitro and in vivo. Mechanistically, IGF2BP3 interacts with RCC2 mRNA and stabilizes the expression of m6A-modified RNA. Thus, we provided compelling evidence demonstrating that the m6A reader IGF2BP3 contributes to tumorigenesis and poor prognosis in AML and can serve as a target for the development of cancer therapeutics.
- 발행기관:
- 생화학분자생물학회
- 분류:
- 생화학