一个由假定 lncRNA HOXB-AS3 编码的肽抑制结肠癌生长。
A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth.
机构信息
Biomedicine Research Center, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Institutes of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
Biomedicine Research Center, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou 511436, China.
出版信息
Mol Cell. 2017 Oct 5;68(1):171-184.e6. doi: 10.1016/j.molcel.2017.09.015.
A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth. Mechanistically, the HOXB-AS3 peptide competitively binds to the ariginine residues in RGG motif of hnRNP A1 and antagonizes the hnRNP A1-mediated regulation of pyruvate kinase M (PKM) splicing by blocking the binding of the ariginine residues in RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, ensuring the formation of lower PKM2 and suppressing glucose metabolism reprogramming. CRC patients with low levels of HOXB-AS3 peptide have poorer prognoses. Our study indicates that the loss of HOXB-AS3 peptide is a critical oncogenic event in CRC metabolic reprogramming. Our findings uncover a complex regulatory mechanism of cancer metabolism reprogramming orchestrated by a peptide encoded by an lncRNA.
大量真核转录本被认为是长非编码 RNA（lncRNA），它们调节着癌症的各种特征。在这里，我们发现 lncRNA HOXB-AS3 编码一个保守的 53 个氨基酸肽。HOXB-AS3 肽（而非 lncRNA）可抑制结肠癌细胞（CRC）的生长。从机制上讲，HOXB-AS3 肽竞争性地结合 hnRNP A1 的 RGG 基序中的精氨酸残基，并通过阻止 hnRNP A1 的 RGG 基序中的精氨酸残基与 PKM 外显子 9 侧翼序列的结合，拮抗 hnRNP A1 对丙酮酸激酶 M（PKM）剪接的调节，从而确保形成低 PKM2，并抑制葡萄糖代谢重编程。HOXB-AS3 肽水平低的 CRC 患者预后较差。我们的研究表明，HOXB-AS3 肽的缺失是 CRC 代谢重编程中关键的致癌事件。我们的发现揭示了由 lncRNA 编码的肽协调的癌症代谢重编程的复杂调控机制。
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