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

Jin-Zhou Huang; Min Chen; De Chen; Xing-Cheng Gao; Song Zhu; Hongyang Huang; Min Hu; Huifang Zhu; Guang-Rong Yan

doi:10.1016/j.molcel.2017.09.015

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.

Authors

Jin-Zhou Huang¹, Min Chen², De Chen², Xing-Cheng Gao³, Song Zhu², Hongyang Huang³, Min Hu², Huifang Zhu², Guang-Rong Yan⁴

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.

MeSH terms

Alternative Splicing
Amino Acid Motifs
Animals
Binding, Competitive
Cell Line, Tumor
Cell Transformation, Neoplastic / genetics*
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
Colonic Neoplasms / genetics*
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology
Exons
Gene Expression Regulation, Neoplastic*
HeLa Cells
Heterogeneous Nuclear Ribonucleoprotein A1
Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics*
Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
Heterografts
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Peptides / antagonists & inhibitors
Peptides / genetics*
Peptides / metabolism
Protein Binding
Protein Interaction Mapping
Pyruvate Kinase / genetics
Pyruvate Kinase / metabolism
RNA, Long Noncoding / antagonists & inhibitors
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction

Substances

Heterogeneous Nuclear Ribonucleoprotein A1
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Peptides
RNA, Long Noncoding
RNA, Small Interfering
Pyruvate Kinase