2. Academic Validation
  3. A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth

A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth

  • Mol Cell. 2017 Oct 5;68(1):171-184.e6. doi: 10.1016/j.molcel.2017.09.015.
Jin-Zhou Huang 1,  Min Chen 2,  De Chen 2,  Xing-Cheng Gao 3,  Song Zhu 2,  Hongyang Huang 3,  Min Hu 2,  Huifang Zhu 2,  Guang-Rong Yan 4
Affiliations

Affiliations

  • 1 Biomedicine Research Center, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; Institutes of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
  • 2 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.
  • 3 Biomedicine Research Center, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
  • 4 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. Electronic address: [email protected].
PMID: 28985503 DOI: 10.1016/j.molcel.2017.09.015
Abstract

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.

Keywords

PKM splicing; cancer metabolism; colon cancer; lncRNA; peptide.

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