Objective: To investigate the clinical significance and pathogenesis of
heterogeneous nuclear ribonucleoprotein U (
hnRNP U) in
acute myeloid leukemia (AML) . Methods: The expression of
hnRNP U, an
RNA binding protein, in patients with AML and healthy controls was compared based on the Gene Expression Profiling Interactive Analysis database and the data of the center. The Beat AML Dataset (n=158) was downloaded from the cBioPortal database. The
hnRNP U expression level was divided into the high-expression group (n=89) and low-expression group (n=69) , and patients' clinical characteristics were compared. The effect of
hnRNP U on the
biological behavior of human AML cell lines was studied by Cell Counting Kit-8 assay to detect cell proliferation.
Annexin Ⅴ-APC/7-AAD
antibodies were used to detect cell apoptosis.
DNA content (PI staining) was quantitatively analyzed to detect cell cycle changes, and colony formation experiments were performed to detect cell cloning formation ability after
hnRNP U knockdown in Kasumi-1 and MOLM-13 cells. To study the effect of
hnRNP U knockdown on the DNA damage response (DDR) pathway
proteins of cleaved-PARP, immunoblot analysis using p-H2A.X was conducted. Results: ①Pan-
cancer analysis showed that
hnRNP U was highly expressed in patients with AML, and the expression level of
hnRNP U mRNA in peripheral blood mononuclear cells was significantly higher in patients with AML than in healthy controls (0.0315±0.0042 vs 0.0195±0.0006, respectively, P<0.01) . ②The age of onset was 56 (2-87) years in the high-expression group and 65 (8-85) years in the low-expression group (t=-2.681, P=0.007) . Moreover, the high-expression group had a higher proportion of combined FLT3 mutations than the low-expression group (χ(2)=4.069, P=0.044) . ③Compared with the negative control,
hnRNP U knockdown inhibited the proliferation (P<0.001 and P<0.001) , promoted the apoptosis (P<0.01 and P<0.001) , decreased the colony formation ability (P<0.001 and P<0.001) , and arrested the cell cycles in the G(2)/M phase (P<0.05 and P<0.01) of Kasumi-1 and MOLM-13 cells, respectively. ④hnRNP U knockdown could increase the
protein expression of cleaved-PARP and p-H2A.X on the DDR pathway. Conclusion:
hnRNP U is highly expressed in AML, and
hnRNP U knockdown can inhibit the occurrence and development of AML possibly through the activation of the DDR pathway.