MicroRNA-365 induces apoptosis and inhibits invasion of human myeloma cells by targeting homeobox A9 (HOXA9)

Abstract

The aberrant micro-RNA (miR) expression has been reported to play a vital role in proliferation and tumorigenesis and of several human cancers. MicroRNA-365 (miR-365) has been shown to exhibit tumor-suppressive or oncogenic role in several human cancers. Nonetheless, little is known about its growth regulatory role in human multiple myeloma. The present study characterized the regulatory control exercised by miR-365 in multiple myeloma. The results showed significant (P < 0.05) upregulation of miR-365 in myeloma tissues and cell lines. Overexpression of miR-365 significantly (P < 0.05) suppressed the proliferation and inhibition of miR-365 promoted the proliferation of the human myeloma cells. The tumor-suppressive effects of miR-365 were found to be the result of apoptosis in the IM-9 myeloma cells. The miR-365 overexpression also suppressed the invasion of the IM-9 myeloma cells. The homeobox gene, HOXA9 was identified as the molecular regulatory target of miR-365 in human myeloma. The overexpression of miR-365 was shown to cause suppression of HOXA9. The silencing of HOXA9 could also suppress the growth of the IM-9 myeloma cells while as the overexpression of HOXA9 could abolish the tumor-suppressive effects of miR-365. The in vivo study revealed that miR-365 inhibits the growth of the xenografted tumors. Nonetheless, the inhibition of miR-365 promotes the growth of the xenografted tumors. To sum up, the current study suggests the tumor-suppressive effects of miR-365 in human myeloma and highlights the applicability of miR-365 as vital therapeutic target against this fatal malignancy.