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Published on: December 13, 2018
lncRNA MSTRG.29039.1 Promotes Proliferation by Sponging hsa-miR-12119 via JAK2/STAT3 Pathway in Multiple Myeloma
Zhaoyun Liu1, Mei Han1, Nanhao Meng1
1Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Abstract:
Noncoding RNA (ncRNA) is involved in the occurrence, development, metastasis, and drug resistance of tumors and involves a variety of biological functions. In addition, miRNA can regulate proliferation and migration and even regulate epigenetics to promote the development of multiple myeloma (MM). However, the mechanism of ncRNA involved in MM is still unclear, and there are many unknown ncRNAs to be explored. This research is aimed at discovering the unknown lncRNA in MM through high-throughput sequencing and to study the mechanism and role of competitive endogenous RNA (ceRNA) involved in the pathogenesis of MM for the development of novel molecular markers and potential new targeted drugs. We screened out 262 new lncRNAs with statistical differences by RNA sequencing and selected the lncRNA MSTRG.29039.1 according to the expression and function of lncRNAs and their target genes in MM. We verified that MSTRG.29039.1 and its target gene OSMR were highly expressed in MM. After knockdown of MSTRG.29039.1 in MM cell lines, the expression of OSMR was decreased, and the expression of hsa-miR-12119 was upregulated which can also promote cell apoptosis and inhibit proliferation. Then, we knocked down hsa-miR-12119 and MSTRG.29039.1, we found that apoptosis of MM cells was reduced, and cell proliferation was increased compared with just knocking down hsa-miR-12119. We further verified the direct binding relationship between MSTRG.29039.1 and OSMR by the dual-luciferase reporter assay system. Thus, MSTRG.29039.1 can competitively bind with miRNA to counteract the inhibitory effect of miRNA on OSMR, which regulates cell proliferation and apoptosis through the JAK2/STAT3 pathway. In a conclusion, lncRNA MSTRG.29039.1 could promote proliferation by sponging hsa-miR-12119 via the JAK2/STAT3 pathway in multiple myeloma. This may be a molecular marker and a potential therapeutic target for MM.
Insights
New research identifies a long noncoding RNA (lncRNA), MSTRG.29039.1, that promotes multiple myeloma (MM) cell proliferation by sponging hsa-miR-12119 via the JAK2/STAT3 pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Noncoding RNAs (ncRNAs) play crucial roles in tumor development, including multiple myeloma (MM).
- The precise mechanisms of ncRNA involvement in MM pathogenesis and potential therapeutic targets remain largely unexplored.
- MicroRNAs (miRNAs) regulate proliferation, migration, and epigenetics, contributing to MM progression.
Purpose of the Study:
- To discover novel long noncoding RNAs (lncRNAs) in MM using high-throughput sequencing.
- To investigate the mechanism and role of competitive endogenous RNA (ceRNA) networks in MM pathogenesis.
- To identify potential molecular markers and therapeutic targets for MM.
Main Methods:
- High-throughput RNA sequencing to screen differentially expressed lncRNAs in MM.
- Selection and validation of lncRNA MSTRG.29039.1 and its target gene OSMR in MM cell lines.
- Knockdown experiments, dual-luciferase reporter assays, and pathway analysis (JAK2/STAT3).
Main Results:
- Identified 262 differentially expressed lncRNAs; selected MSTRG.29039.1 for further study.
- MSTRG.29039.1 and OSMR were highly expressed in MM; knockdown of MSTRG.29039.1 decreased OSMR and upregulated hsa-miR-12119.
- MSTRG.29039.1 sponges hsa-miR-12119, promoting MM cell proliferation and inhibiting apoptosis via the JAK2/STAT3 pathway.
Conclusions:
- lncRNA MSTRG.29039.1 promotes proliferation in multiple myeloma by sponging hsa-miR-12119 through the JAK2/STAT3 pathway.
- MSTRG.29039.1 acts as a ceRNA, counteracting miRNA inhibition of its target gene OSMR.
- MSTRG.29039.1 represents a potential molecular marker and therapeutic target for MM.
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