miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells.
miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells.
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DOI：
10.18632/oncotarget.3025
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Aqeilan RI
中科院分区：
文献类型：
--
作者：
Salah Z;Arafeh R;Maximov V;Galasso M;Khawaled S;Abou-Sharieha S;Volinia S;Jones KB;Croce CM;Aqeilan RI
骨肉瘤（Osteosarcoma， OS）是青少年和年轻人最常见的原发性恶性骨肿瘤。骨肉瘤发生和进展的基本机制仍然不清楚。MicroRNAs （miRNAs）在细胞发育和肿瘤中具有深远的影响。我们最近报道了独特的miRNA特征与OS的发病和进展有关。特别有趣的是，我们发现miR-27a的高表达与临床转移性疾病相关。我们在这里报道过表达miR-27a/miR-27a*，一个来源于单一前体的microRNA对，促进肺OS转移形成。相比之下，通过海绵技术分离miR-27a/miR-27a*抑制了OS细胞的侵袭和转移形成。miR-27a/miR-27a*直接抑制CBFA2T3在其他靶基因中的表达。我们证明CBFA2T3在大多数OS样本中下调，其过表达显著减弱了miR-27a/miR-27a*介导的OS转移过程，这表明CBFA2T3在OS中具有肿瘤抑制作用。这些研究结果表明，miR-27a/miR-27a*对在OS转移中发挥重要作用，并提出其作为治疗OS转移的潜在诊断和治疗靶点。
Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer. We recently reported that unique miRNA signatures associate with the pathogenesis and progression of OS. Of particular interest, we found that higher expression of miR-27a is associated with clinical metastatic disease. We report here that overexpression of miR-27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge technology suppressed OS cells invasion and metastases formation. miR-27a/miR-27a* directly repressed CBFA2T3 expression among other target genes. We demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over expression significantly attenuated OS metastatic process mediated by miR-27a/miR-27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.
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影响因子：
50.3
作者：
Gruber TA;Larson Gedman A;Zhang J;Koss CS;Marada S;Ta HQ;Chen SC;Su X;Ogden SK;Dang J;Wu G;Gupta V;Andersson AK;Pounds S;Shi L;Easton J;Barbato MI;Mulder HL;Manne J;Wang J;Rusch M;Ranade S;Ganti R;Parker M;Ma J;Radtke I;Ding L;Cazzaniga G;Biondi A;Kornblau SM;Ravandi F;Kantarjian H;Nimer SD;Döhner K;Döhner H;Ley TJ;Ballerini P;Shurtleff S;Tomizawa D;Adachi S;Hayashi Y;Tawa A;Shih LY;Liang DC;Rubnitz JE;Pui CH;Mardis ER;Wilson RK;Downing JR
通讯作者：
Downing JR
影响因子：
3.7
作者：
Barrett CW;Smith JJ;Lu LC;Markham N;Stengel KR;Short SP;Zhang B;Hunt AA;Fingleton BM;Carnahan RH;Engel ME;Chen X;Beauchamp RD;Wilson KT;Hiebert SW;Reynolds AB;Williams CS
通讯作者：
Williams CS
影响因子：
11.2
作者：
Jones KB;Salah Z;Del Mare S;Galasso M;Gaudio E;Nuovo GJ;Lovat F;LeBlanc K;Palatini J;Randall RL;Volinia S;Stein GS;Croce CM;Lian JB;Aqeilan RI
通讯作者：
Aqeilan RI
影响因子：
48
作者：
Ebert, Margaret S.;Neilson, Joel R.;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.
影响因子：
5.3
作者：
Chyla, Brenda J.;Moreno-Miralles, Isabel;Hiebert, Scott W.
通讯作者：
Hiebert, Scott W.