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

Abstract

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.

Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

“…Multiple myeloma (MM) is a kind of neoplastic plasma-cell disorder, characterized by the immersion of malignant plasma cells into bone marrow and still incurable [1,2]. The survival terms of patients with MM range from a few weeks to more than 10 years with the five-year survival rate of 40 %.…”

“…The survival terms of patients with MM range from a few weeks to more than 10 years with the five-year survival rate of 40 %. Etiologies and potential molecular mechanisms of MM are still poorly understood, which results in complicated therapies [1,3,4]. In spite of advanced progress in diagnosis and treatment, including immunomodulatory medicine, proteasome inhibitors and autologous stem cell transplantation, the prognosis of MM is also dismal.…”

Integrating multiple‐level molecular data to infer the distinctions between glioblastoma and lower‐grade glioma

“…Specially, we found that AKT2 had a somatic mutation in LGG patients; however, GBM patients did not carry any mutations on AKT2 . In addition, AKT2 interacted with lncRNA MALAT1 (ENSG00000251562), which is a famous cancer‐associated lncRNA . AKT3 interacted with lncRNA TUG1 (ENSG00000253352), which also plays an important role in various kinds of cancer .…”

The role of long non‐coding RNAs in multiple myeloma

“…Furthermore, the knockdown of MALAT1 induces apoptosis in MM cells through an endogenous apoptotic pathway by downregulating Bcl‐2 and upregulating Bax. On the other hand, MALAT1 can regulate MM cell autophagy by binding to high mobility group box 1 (HMGB1) at the post‐translational level . HMGB1 is a kind of DNA‐binding protein closely correlated to hematological malignancies, including lymphoma and MM, and contributes to the growth and proliferation of MM cells .…”