[The Clinical Significance and in vitro Experimental Study of hnRNP U in Multiple Myeloma]

To analyze the expression level of heterogeneous nuclear ribonucleoprotein U (hnRNP U) and its correlation with prognosis in patients with multiple myeloma (MM), and explore the functional role as well as molecular mechanism of hnRNP U, thereby providing a theoretical basis for development of hnRNP U as a novel therapeutic target for MM.

Based on Gene Expression Omnibus (GEO) database, the expression of hnRNP U in plasma cell diseases and healthy controls was compared. Based on the GSE9782 dataset (n =264), patients were divided into high expression group (n =114) and low expression group (n =150) according to the median expression level of hnRNP U . Overall survival (OS) between the two groups was compared. RPMI 8226, NCI-H929 and MM.1S cell lines were selected as tool cell lines. Following knockdown of hnRNP U by shRNA, the cell proliferation was detected by CCK-8. The apoptosis of MM cells was analyzed by Annexin V/7-AAD staining, and cell cycle was detected by BrdU/DAPI staining followed by flow cytometric analysis. The effect of hnRNP U on the biological characteristics of human MM cells was explored. The effect of knockdown of hnRNP U on DNA damage response pathways was analyzed by Western blot.

Analysis of GSE5900 and GSE2113 datasets showed that the mRNA level of hnRNP U rose with the increased degree of malignancy of plasma cell diseases. Survival curve analysis of GSE9782 dataset showed that the high expression group of hnRNP U had a shorter OS than that of the low expression group. Down-regulation of hnRNP U in MM cell lines RPMI 8226, NCI-H929 and MM.1S could inhibit the cell proliferation, promote cell apoptosis and arrest the cell cycle. After knocking down hnRNP U, the expression levels of cleaved PARP and p-H2A.X, as the important markers of activated DNA damage pathway, were significantly increased in MM cells.

hnRNP U is highly expressed in several plasma cell diseases including MM, and the high expression of hnRNP U in MM patients predicts poor prognosis. Knocking down hnRNP U can inhibit the malignant progression of MM cells, which is possibly associated with aggravated DNA damage.