PCAT-1 promotes cell growth by sponging miR-129 via MAP3K7/NF-κB pathway in multiple myeloma.

ABSTRACT

Loss of one or some specific miRNA-mediated regulation is closely associated with malignant progression of multiple myeloma (MM). But how these miRNAs work and what role the specific miRNA plays in this process of malignant progression remain unclear. It was found in this study that the expression of miR-129 was decreased in both MM cell lines and newly diagnosed MM patients. Further clinicopathological statistics showed that miR-129 was correlated with the isotype of MM patients. MiR-129 overexpression disturbed cell proliferation, cell cycle evolution and spurred apoptosis both in vitro and in vivo. MAP3K7, a kinase able to activate NF-κB circuit, was found to be up-regulated in MM and contain a binding target of miR-129. In addition, lncRNA PCAT-1 functioned to sponge miR-129 and thereby lowered its expression. PCAT-1 knockdown eliminated the tumour-promoting effect caused by miR-129 inhibition, probably through repressing MAP3K7 and subsequent NF-κB activation. To the best of our knowledge, this is the first study to have discovered that increased expression of PCAT-1 could augment cell proliferation and cycle procession and inhibit apoptosis by down-regulating miR-129 via the MAP3K7/NF-κB pathway in MM.