title: 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.
authors.affiliation: Department of Hematology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, China.
authors.forename: Da
authors.identifier: 0000-0001-6551-8458
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of medicine, New District Hospital of Hohhot City, Hohhot, 010050, China.
authors.forename: Ai-E
authors.initials: AE
authors.lastname: Lv
authors.affiliation: Department of Hematology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Li
authors.affiliation: Department of Hematology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, China.
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Han
authors.affiliation: Department of Hematology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, China.
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D005260:Female; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C557041:MALAT1 long non-coding RNA, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm
keywords: AUTOPHAGY; HMGB1; MALAT-1; MULTIPLE MYELOMA