lncRNA MSTRG.29039.1 Promotes Proliferation by Sponging hsa‐miR‐12119 via JAK2/STAT3 Pathway in Multiple Myeloma

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.

Identification and evaluation of a six-lncRNA prognostic signature for multiple myeloma

“…Subsequent analysis using a robust likelihood-based survival model was used to filter the candidate pool to 15 lncRNAs with the lowest P values and then to six lncRNAs with the lowest Akaike information criterion (AIC) values. These six lncRNAs demonstrated predictive potential for 5-year overall survival in MM patients across both the training and validation sets, indicating their potential utility as prognostic biomarkers in clinical practice [ 25 – 28 ].…”

The Expression of Serum lncRNA MIR17HG in Patients with Multiple Myeloma and Its Clinical Significance

“…MM represents the most common hematological cancer in the world and is further associated with an ever-increasing incidence year by year [19]. Te hard-done work of our peers recently unveiled that lncRNAs are implicated in tumorigenesis, progression, metastasis, and drug resistance [20]. Additionally, evidence has come to light indicating that MIR17HG exerts a potential function in cancer biology [21].…”

Long non‑coding RNAs in multiple myeloma (Review)

“…The RNA component of mitochondrial RNA processing endoribonuclease (RMRP) may regulate cell proliferation through the RMRP/miR-34a-5p/c-Myc pathway, and c-Myc locates in the RMRP promoter region to promote RMRP transcription, forming a circular pathway (28). In addition to these 'hot spot' lncRNA studies, numerous newly discovered lncRNAs have a cancer-promoting effect in MM.MSTRG.29039.1 reduces the inhibitory effect of miR-12119 on the oncostatin M receptor (OSMR), and OSMR upregulation activates the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, forming the MSTRG.29039.1/miR-12119/OSMR/JAK2/STAT3 pathway (29). RP11-301G19.1 upregulates high-mobility group protein B2 (HMGB2), the target gene of miR-582-5p, promotes the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and activates the RP11-301G19.1/miR-582-5p/PI3K/Akt pathway (30).…”