The Role Of HNRPDL In Malignant Cells

Objective: This study aims to delineate the roles of heterogeneous nuclear ribonucleoprotein D-like(HNRPDL) in malignant cells(colorectal cancer and chronic myeloid leukemia).Methods:(1) The retroviral vectors to over-express and knockdown HNRPDL were constructed, malignant cell(e.g. SW620 and K562) were transduced with these viruses, and then the transcript and protein expression of HNRPDL were detected with Q-RT-PCR and western blot.(2) The effects of HNRPDL manipulation on cell proliferation, migration, cell cycle, colony-forming cell(CFC) capacity and tumorigenic ability were investigated.(3) The effect of HNRPDL on the response of K562 cell in treatment of Imatinib mesylate(IM) was assessed.(4) BaF3 cells were transduced with both BCR/ABL and HNRPDL, the growth and CFC capacity of these cells were compared with the cells transduced with each gene.Results:(1) The expression of HNRPDL was significantly higher in colorectal cancer tissues compared to control normal tissues. HNRPDL silencing in SW620 cells(colorectal cancer) inhibited their growth, migration and CFC. Moreover, the silence of HNRPDL suppressed the tumorigenic ability of SW620 cells(control group: 8/8,HNRPDL knockdown group: 5/8).(2) The cell cycle analyses showed that silence of HNRPDL in SW620 cells increased the proportion of cells in G0/G1 phase and decreased cells in G2/M phase. Western blot showed the expression of cyclin D3 was inhibited by HNRPDL silencing in SW620 cells.(3) We found the expression of HNRPDL in CD34+ cells from chronic myeloid leukemia(CML) patients was significantly higher than those from healthy donors. Silence of HNRPDL inhibited the growth of K562, MEG-01 and BV173 cells as well as CD34+ cells from patients. The silence of HNRPDL suppressed the tumorigenic abilities of MEG-01 cells(controlgroup: 6/8; shHNRPDL#1 group:1/8; shHNRPDL#2 group: 0/8) in nude mice; in addition, the growth of the tumors from shHNRPDL group was slower than those from the control group.(4) Overexpression of HNRPDL promoted the growth and CFC of both K562 and BaF3 cells, it also sensitized BaF3 cells in treatment of mIL-3.BCR/ABL and HNRPDL co-transduced BaF3 cells grew faster and produced more CFCs than BCR/ABL or HNRPDL alone transduced cells.(5) Silence of HNRPDL sensitized K562 cells in treatment of IM, however overexpression of HNRPDL conferred IM resistance.Conclusion:(1) HNRPDL is up-regulated in colorectal cancer samples. Silence of HNRPDL inhibits the growth of SW620 cells in vitro and in vivo and reduces the expression of cyclin D3. The cell cycle is arrested in G0/G1 phase.(2) The expression of HNRPDL in both nucleated cells and CD34+ cells from chronic myeloid leukemia(CML) patients is significantly higher than those from healthy donors. Silence of HNRPDL also inhibits the growth, CFC capacities and tumorigenic ability of CML cells. HNRPDL overexpression promotes the growth of K562 cells and synergizes with BCR/ABL to promote the growth of BaF3 cells. In addition, HNRPDL modulates IM response of CML cells.