Large-scale screening identifies a novel microRNA, miR-15a-3p, which induces apoptosis in human cancer cell lines.
Large-scale screening identifies a novel microRNA, miR-15a-3p, which induces apoptosis in human cancer cell lines.
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DOI：
10.4161/rna.23339
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发表时间：
2013-02-01
期刊：
影响因子：
4.1
通讯作者：
Shiloach, Joseph
中科院分区：
文献类型：
--
作者：
Druz, Aliaksandr;Chen, Yu-Chi;Shiloach, Joseph
MicroRNAs （miRNAs）已被发现参与癌症的发生、进展和转移，因此已被建议作为癌症检测和治疗的工具。在这项工作中，对完整miRNA模拟物文库的大规模筛选表明，hsa-miR-15a-3p在以下人类癌细胞中具有促凋亡作用：HeLa， AsPc-1, MDA-MB-231, KB3, ME180， HCT-116和A549。miR-15a -3p是促凋亡miRNA簇的新成员miR-15a/16，它被发现激活Caspase-3/7并导致B/CMBA的生存能力丧失。初步筛选时的Ov细胞。随后的微阵列和生物信息学分析确定了以下四个抗凋亡基因：bcl2l1、naip5、fgfr2和mybl2，它们可能是B/CMBA中mmu-miR-15a-3p的靶点。Ov细胞。后续研究证实了hsa-miR-15a-3p在人细胞中的促凋亡作用，其能够激活Caspase-3/7，降低细胞活力，抑制HeLa和AsPc-1细胞中bcl2l1 （bcl-xL）的表达。研究还发现，MiR-15-3p可降低HEK293、MDA-MB-231、KB3、ME180、HCT-116和A549细胞系的生存能力，因此，MiR-15-3p可被考虑用于Bcl-xL高表达相关癌症（宫颈癌、胰腺癌、乳腺癌、肺癌和结直肠癌）的细胞凋亡调节疗法。hsa-miR-15a-3p在这些肿瘤中诱导细胞凋亡的能力可能取决于Bcl-xL的表达水平。与使用人工反义寡核苷酸相比，使用内源性bcl-xL抑制剂和其他抗凋亡基因（如hsa-miR-15a-3p）可能为癌症治疗中的凋亡调节疗法提供更好的选择。
MicroRNAs (miRNAs) have been found to be involved in cancer initiation, progression and metastasis and, as such, have been suggested as tools for cancer detection and therapy. In this work, a large-scale screening of the complete miRNA mimics library demonstrated that hsa-miR-15a-3p had a pro-apoptotic role in the following human cancer cells: HeLa, AsPc-1, MDA-MB-231, KB3, ME180, HCT-116 and A549. MiR-15a-3p is a novel member of the pro-apoptotic miRNA cluster, miR-15a/16, which was found to activate Caspase-3/7 and to cause viability loss in B/CMBA.Ov cells during preliminary screening. Subsequent microarrays and bioinformatics analyses identified the following four anti-apoptotic genes: bcl2l1, naip5, fgfr2 and mybl2 as possible targets for the mmu-miR-15a-3p in B/CMBA.Ov cells. Follow-up studies confirmed the pro-apoptotic role of hsa-miR-15a-3p in human cells by its ability to activate Caspase-3/7, to reduce cell viability and to inhibit the expression of bcl2l1 (bcl-xL) in HeLa and AsPc-1 cells. MiR-15-3p was also found to reduce viability in HEK293, MDA-MB-231, KB3, ME180, HCT-116 and A549 cell lines and, therefore, may be considered for apoptosis modulating therapies in cancers associated with high Bcl-xL expression (cervical, pancreatic, breast, lung and colorectal carcinomas). The capability of hsa-miR-15a-3p to induce apoptosis in these carcinomas may be dependent on the levels of Bcl-xL expression. The use of endogenous inhibitors of bcl-xL and other anti-apoptotic genes such as hsa-miR-15a-3p may provide improved options for apoptosis-modulating therapies in cancer treatment compared with the use of artificial antisense oligonucleotides.