The mechanism study of miR-125b in occurrence and progression of multiple myeloma.

Although many efforts have contributed to improve our knowledge of molecular pathogenesis about multiple myeloma (MM), the role and significance of microRNAs and long noncoding RNAs in MM cells, along with the core mechanism remains virtually absent. The mRNA levels of miR-125b and MALAT1 in MM cell lines were detected by qRT-PCR. The influence of Lenti-Sh-miR-125b on cell viability and the Notch-1 pathway-related proteins were assessed by MTT method and western blot, respectively. We also investigated the regulation effect between MALAT1 and Notch1 pathway. Moreover, the connection between Notch1 signaling and MM cell growth was discussed in-depth. The reverse effect of pcDNA-Notch1 on the cell viability and Notch-1 pathway proteins induced by Si-MALAT1 was also studied. Furthermore, miR-125b overexpressing MM cell lines were injected subcutaneously into nude mice. MiR-125b and MALAT1 were inversely expressed in MM cell lines. Lenti-Sh-miR-125b inhibited the expression of MALAT1 and Notch-1 protein. Binding sites were confirmed between miR-125b and MALAT1, and silencing MALAT1 did not alter the expression of Notch-1. The apoptosis rate was increased and the survival rate was decreased obviously in GSI XII (targeted cleavage of Notch-1 receptor) group, along with the inhibited Notch1 and HES1 proteins. Moreover, the decreased cell viability and Notch-1 pathway proteins induced by Si-MALAT1 could be reversed by pcDNA-Notch1. Lenti-Sh-miR-125b promoted survival and decreased Notch1 and HES1 proteins levels, while this effect was reversed by si -MALAT1. MiR-125b regulated MALAT1 expression via Notch1 signaling pathway to regulate cell growth, thus participating in the occurrence and progression of MM, which functioned as a therapeutic target for tracking MM.

LncRNA MALAT-1 Elevates HMGB1 to Promote Autophagy Resulting in Inhibition of Tumor Cell Apoptosis in Multiple Myeloma.

Long non-coding RNAs (lncRNAs) can participate in the pathological process of multiple myeloma (MM) via regulation of specific gene expression and function. This research aimed to study the role of MALAT-1 and the underlying mechanism in MM. In this study, the expression of MALAT-1 and HMGB1 protein in the bone marrow mononuclear cells from MM patients at different stages and in MM cell lines was determined by qRT-PCR and western blot, respectively. The endogenous expression of MALAT-1 and HMGB1 was modulated using lentivirus vectors transfection. CHX chase assay and RIP analyses were performed to explore the interaction between MALAT-1 and HMGB1 in MM. Nude mouse xenograft was made and used for in vivo experiment study. The expression of MALAT-1 and HMGB1 in the bone marrow mononuclear cells from patients with untreated multiple myeloma was dramatically increased, as well as in MM cell lines, KM3 and U266; while MALAT-1 expression and HMGB1 protein level both decreased significantly in complete remission patients. Furthermore, MALAT-1 knockdown facilitated the degradation of HMGB1 at the post-translational level via increase of the ubiquitination of HMGB1 in MM cells. MALAT-1 was shown to promote autophagy in MM through upregulation of HMGB1. In vivo, MALAT-1 knockdown could inhibit tumor growth significantly in tumor-bearing mice and reduced the protein expressions of HMGB1, Beclin-1, and LC3B in tumor tissues. LncRNA MALAT-1 increases the expression level of HMGB1 in MM thereby promotes autophagy resulting in the inhibition of apoptosis. J. Cell. Biochem. 118: 3341-3348, 2017. © 2017 Wiley Periodicals, Inc.