Long noncoding RNA UCA1 regulates proliferation and apoptosis in multiple myeloma by targeting miR-331-3p/IL6R axis for the activation of JAK2/STAT3 pathway
| Autor: | J-L, Li, X-L, Liu, S-F, Guo, Y, Yang, Y-L, Zhu, J-Z, Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
Down-Regulation Apoptosis Janus Kinase 2 Transfection Receptors Interleukin-6 Xenograft Model Antitumor Assays Up-Regulation Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-myc MicroRNAs Proto-Oncogene Proteins c-bcl-2 Cell Line Tumor Humans Cyclin D1 RNA Long Noncoding Multiple Myeloma Cell Proliferation Signal Transduction bcl-2-Associated X Protein |
| Zdroj: | European review for medical and pharmacological sciences. 23(21) |
| ISSN: | 2284-0729 |
| Popis: | We attempted to clarify the regulatory mechanism of UCA1/miR-331-3p/IL6R on cell progression in multiple myeloma (MM).The expression of UCA1, miR-331-3p, and IL6R in tumor tissues and cells was measured by qRT-PCR. Cell Counting Kit-8 (CCK-8) was conducted to detect cell proliferation, and flow cytometry assay was applied to examine cell apoptosis. Protein expression of L6R, p-JAK2, p-STAT3, c-Myc, CyclinD1, Bcl-2, and Bax was detected by Western blot assay. The interaction among miR-331-3p, UCA1, and IL6R was determined by Luciferase reporter system. Murine xenograft assay was performed to confirm the biological function of UCA1 in vivo.The expression of UCA1 and IL6R was up-regulated, while miR-331-3p was down-regulated in MM tumors and cell lines compared with normal tissues and cells. By calculation, miR-331-3p was correlated with UCA1 or IL6R inversely. In addition, UCA1 knockdown suppressed cell proliferation and promoted apoptosis in vitro and in vivo. Luciferase reporter system confirmed the interaction between miR-331-3p and UCA1 or IL6R. More importantly, UCA1 restored miR-331-3p mediated inhibition of proliferation and promotion on apoptosis of MM cells. Consistently, IL6R rescued UCA1 knockdown caused repression on MM cell growth and elevation on apoptosis. Besides, UCA1 facilitated the activation of the JAK2/STAT3 signaling pathway by enhancing IL6R expression via targeting miR-331-3p.UCA1 accelerates proliferation and suppresses apoptosis in MM by targeting miR-331-3p/IL6R axis to activate JAK2/STAT3 pathway, providing potential targets for the diagnosis and therapy of MM. |
| Databáze: | OpenAIRE |
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