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Updated: Jan 12, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
The impact of STAiR18 on multiple myeloma survival rates
Yingmiao Wu1,2, Haolin Wang1,2, Ji Luo1,2
1Genetic Diseases Key Laboratory of Sichuan Province, Department of Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Background:
A subset of multiple myeloma (MM) patients exhibited worse survival and higher tumor burden. STAiR18 has been found to be highly expressed in MM cell lines. However, the precise mechanisms underlying the upstream and downstream regulation of STAiR18 have remained unclear.
Methods:
The expression of STAiR18 and miR-451a in MM patients and cell lines was detected using quantitative reverse transcriptase PCR (qRT-PCR). ChIP-qPCR was performed to assess the enrichment of pSTAT3 at the STAiR18 promoter. The subcellular localization of STAiR18 was determined by FISH. The binding relationship between STAiR18 and miR-451a was predicted through bioinformatics analyses and validated using RNA pull down and dual-luciferase reporter assays. Cell proliferation was evaluated with CCK-8 assay, Edu assay, and flow cytometry. The expression levels of key proteins in the IL-6R/STAT3/JAK2 pathway, along with Cyclin D1 and apoptosis-related markers, were analyzed by Western blot. Cell cycle distribution and apoptosis rate were quantified by flow cytometry. The role of STAiR18 was also investigated in vivo using a xenograft tumor model, which was established by tail vein injection of MM cell lines into NOG mice.
Results:
In MM patients, STAiR18 expression was notably upregulated in myeloma cells from bone marrow, and positively correlated with clinical stage and worse outcome. Knockdown (KD) and overexpression (OE) of STAT3 affected the expression level of STAiR18, and pSTAT3 was significantly enriched in STAiR18's promoter. Knockdown of STAiR18 reduced the proliferation of MM cells in vitro and suppressed tumor growth in vivo. STAiR18 was predicted and confirmed to primarily localize in the cytoplasm. STAiR18 KD resulted in upregulation of miR-451a levels. The binding between STAiR18 and miR-451a (silencing IL-6R) was predicted and validated. Through KD and rescue experiments, we demonstrated that STAiR18 sponged miR-451a, and promoted myeloma cell proliferation via IL-6R/STAT3/JAK2 pathway.
Conclusions:
The study revealed that STAiR18 competed with endogenous miR-451a, and formed a novel positive-feedback loop of IL-6R/STAT3/JAK2 to promote proliferation of MM. These findings suggest that STAiR18 represents a promising novel therapeutic strategy for MM treatment.
Insights
This study reveals STAiR18 promotes multiple myeloma (MM) cell proliferation by sponging miR-451a and activating the IL-6R/STAT3/JAK2 pathway. STAiR18 presents a potential therapeutic target for MM treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multiple myeloma (MM) is associated with poor survival and high tumor burden in a subset of patients.
- High STAiR18 expression in MM cell lines suggests a role in disease progression.
- The regulatory mechanisms of STAiR18 in MM remain largely unknown.
Purpose of the Study:
- To elucidate the upstream and downstream regulatory mechanisms of STAiR18 in multiple myeloma.
- To investigate the role of STAiR18 in MM cell proliferation and tumor growth.
- To explore STAiR18 as a potential therapeutic target for MM.
Main Methods:
- Quantitative reverse transcriptase PCR (qRT-PCR) for gene expression analysis.
- Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) to assess transcription factor binding.
- Fluorescence in situ hybridization (FISH) for subcellular localization.
- Bioinformatics, RNA pull down, and dual-luciferase reporter assays to validate molecular interactions.
- Cell proliferation assays (CCK-8, Edu, flow cytometry) and Western blotting for pathway analysis.
- In vivo xenograft tumor models in NOG mice to evaluate therapeutic efficacy.
Main Results:
- STAiR18 expression is upregulated in MM patient myeloma cells and correlates with advanced clinical stage and poor prognosis.
- pSTAT3 binds to the STAiR18 promoter, indicating STAT3 is an upstream regulator.
- Knockdown of STAiR18 inhibits MM cell proliferation in vitro and tumor growth in vivo.
- STAiR18 acts as a molecular sponge for miR-451a, promoting MM cell proliferation via the IL-6R/STAT3/JAK2 pathway.
Conclusions:
- STAiR18 promotes MM proliferation by sequestering miR-451a and activating the IL-6R/STAT3/JAK2 positive-feedback loop.
- STAiR18 is a promising therapeutic target for multiple myeloma.
- Understanding STAiR18 regulation offers new avenues for MM treatment strategies.
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