State Key Laboratory of Molecular Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
PLoS One. 2010 Feb 25;5(2):e9429. doi: 10.1371/journal.pone.0009429.
microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs at the post-transcriptional stage. Several studies have shown that miRNAs modulate gene expression in mammalian cells by base pairing to complementary sites in the 3'-untranslated region (3'-UTR) of the target mRNAs.
METHODOLOGY/PRINCIPAL FINDINGS: In the present study, miR-24 was found to target fas associated factor 1(FAF1) by binding to its amino acid coding sequence (CDS) region, thereby regulating apoptosis in DU-145 cells. This result supports an augmented model whereby animal miRNAs can exercise their effects through binding to the CDS region of the target mRNA. Transfection of miR-24 antisense oligonucleotide (miR-24-ASO) also induced apoptosis in HGC-27, MGC-803 and HeLa cells.
CONCLUSIONS/SIGNIFICANCE: We found that miR-24 regulates apoptosis by targeting FAF1 in cancer cells. These findings suggest that miR-24 could be an effective drug target for treatment of hormone-insensitive prostate cancer or other types of cancers. Future work may further develop miR-24 for therapeutic applications in cancer biology.
microRNAs (miRNAs) 是一种小的非编码 RNA,在转录后阶段调节同源 mRNAs。多项研究表明,miRNAs 通过与靶 mRNAs 的 3'非翻译区 (3'UTR) 中的互补位点碱基配对,调节哺乳动物细胞中的基因表达。
方法/主要发现: 在本研究中,发现 miR-24 通过与 fas 相关因子 1(FAF1) 的氨基酸编码序列 (CDS) 区域结合,从而调节 DU-145 细胞中的细胞凋亡,靶向 FAF1。这一结果支持了一个增强的模型,即动物 miRNAs 可以通过与靶 mRNA 的 CDS 区域结合来发挥其作用。miR-24 反义寡核苷酸 (miR-24-ASO) 的转染也诱导了 HGC-27、MGC-803 和 HeLa 细胞的凋亡。
结论/意义: 我们发现 miR-24 通过靶向癌细胞中的 FAF1 来调节细胞凋亡。这些发现表明,miR-24 可能成为治疗激素不敏感前列腺癌或其他类型癌症的有效药物靶点。未来的工作可能会进一步开发 miR-24 用于癌症生物学的治疗应用。