MicroRNA-27 Inhibits Autophagy and Promotes Proliferation of Multiple Myeloma Cells by Targeting the NEDD4/Notch1 Axis.

Multiple myeloma (MM) is a malignant tumor disease that seriously affects the health of patients. Previous studies have shown the crucial role of autophagy in the development of MM. Therefore, the study aimed to study the effect of miR-27 on autophagy in MM via NEDD4/Notch1 axis. RT-qPCR or western blot analysis was used to detect the expression of miR-27, NEDD4, and Notch1 in bone marrow tissues and CD138+ plasma cells of patients and MM cells. After gain- and loss-of-function assays in MM cells, proliferation and invasion were assessed by clone formation and Transwell assays. Meanwhile, expression of autophagy-related proteins was measured by western blot analysis, followed by evaluation of autophagosomes and autophagic flow. The targeting relationship was evaluated by luciferase reporter assay, whereas the binding of NEDD4 to Notch1 protein was analyzed by co-immunoprecipitation. The ubiquitination level of Notch1 protein was detected. A nude mouse tumor model was established to determine the role of miR-27 in MM in vivo. miR-27 and Notch1 upregulation and NEDD4 downregulation were observed in bone marrow tissues and CD138+ plasma cells of patients and MM cells. miR-27 negatively targeted NEDD4, while NEDD4 could specifically bind to Notch1 protein to increase Notch1 ubiquitin degradation in MM cells. miR-27 or Notch1 overexpression or NEDD4 silencing diminished autophagy but enhanced proliferation and invasion of MM cells. miR-27 upregulation promoted the formation of subcutaneous tumor in nude mice. Collectively, miR-27 elevated Notch1 expression by targeting NEDD4 and promoted the development of MM by inhibiting cell autophagy, which provides a new idea and basis for MM treatment.

Increased expression of miR-27 predicts poor prognosis and promotes tumorigenesis in human multiple myeloma.

Multiple myeloma (MM) is an incurable hematological malignancy characterized by abnormal infiltration of plasma cells in the bone marrow. MicroRNAs (miRNAs) have emerged as crucial regulators in human tumorigenesis and tumor progression. miR-27, a novel cancer-related miRNA, has been confirmed to be implicated in multiple types of human tumors; however, its biological role in MM remains largely unknown. The present study aimed to characterize the biological role of miR-27 in MM and elucidate the potential molecular mechanisms. Here we found that miR-27 was significantly up-regulated in MM samples compared with normal bone marrow samples from healthy donors. Moreover, the log-rank test and Kaplan-Meier survival analysis displayed that MM patients with high miR-27 expression experienced a significantly shorter overall survival than those with low miR-27 expression. In the current study, we transfected MM cells with miR-27 mimics or miR-27 inhibitor to manipulate its expression. Functional studies demonstrated that miR-27 overexpression promoted MM cell proliferation, facilitated cell cycle progression, and expedited cell migration and invasion; whereas miR-27 knockdown inhibited cell proliferation, induced cell cycle arrest, and slowed down cell motility. Mechanistic studies revealed that Sprouty homolog 2 (SPRY2) was a direct target of miR-27 and that rescuing SPRY2 expression reversed the promoting effects of miR-27 on MM cell proliferation, migration, and invasion. Besides, miR-27 ablation suppressed tumorigenecity of MM cells in mouse xenograft models. Collectively, our data indicate that miR-27 exerts its oncogenic functions in MM by targetting SPRY2 and that miR-27 may be used as a promising candidate target in MM treatment.

[Determination of serum granulocyte colony-stimulating factor level in patients with chronic idiopathic neutropenia and its significance].

To investigate the serum granulocyte colony-stimulating factor (G-CSF) level in patients with chronic idiopathic neutropenia (CIN) and analyze its clinical significance. By the use of G-CSF-specific enzyme-linked immunosorbent assay (ELISA), the serum levels of G-CSF were determined in 40 cases with chronic CIN, 40 cases with systemic lupus erythematosus (SLE) complicated neutropenia and 40 healthy volunteer (normal control). Results showed that serum G-CSF was positive in 11 normal controls and in 10 cases with SLE, and the G-CSF levels were (27.34 +/- 8.00) ng/L and (26.76 +/- 7.26) ng/L, respectively. Serum G-CSF in 27 cases with CIN was positive, the level was (134.04 +/- 89.29) ng/L, which was higher than that in the normal controls and the cases with SLE (P < 0.01). It was concluded that an obstacle to utilization of G-CSF could be existed in the patients with CIN.