Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells

被引：70

作者：

Hao, Mu ^{[1
,2
,3
]}

Zhang, Li ^{[4
]}

An, Gang ^{[1
,2
,3
]}

Sui, Weiwei ^{[1
,2
,3
]}

Yu, Zhen ^{[1
,2
,3
]}

Zou, Dehui ^{[1
,2
,3
]}

Xu, Yan ^{[1
,2
,3
]}

Chang, Hong ^{[5
]}

Qiu, Lugui ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China

[2] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China

[3] Peking Union Med Coll, Tianjin, Peoples R China

[4] Sichuan Univ, Blood Sect, W China Hosp, Chengdu 610064, Sichuan, Peoples R China

[5] Univ Toronto, Univ Hlth Network, Dept Lab Hematol, Toronto, ON M5S 1A1, Canada

来源：

JOURNAL OF HEMATOLOGY & ONCOLOGY | 2011年 / 4卷

基金：

中国国家自然科学基金;

关键词：

MULTIPLE-MYELOMA; MICRORNAS; DISEASE;

D O I：

10.1186/1756-8722-4-37

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of myeloma (MM) cells. This study identified that microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC) with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells. Interleukin-6 (IL-6) produced by BMSCs suppressed the expression of miRNA-15a and 16 in a time- and dose- dependent pattern, with the suppression on miRNA-15a being more significant than on miRNA-16. miRNA-15a-transfected MM cells were found to be arrested in G1/S checkpoint, and the transfected MM cells had decreased growth and survival. In conclusion, our data suggest that via suppressing miRNA-15a and -16 expressions, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells.

引用

页数：3

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