title: An Amphiphilic Peptide Induces Apoptosis Through the miR29b-p53 Pathway in Cancer Cells.
abstract: Peptides have been in the limelight, as therapeutic agents for cancer treatment through various applications due to their high target selectivity and exceptional ability to penetrate the cell membrane. Recent studies have revealed that synthesized peptides bind to hairpin structures of RNA that affect their activities such as changing the efficacy of microRNA maturation. MicroRNA-mediated p53 activation by the microRNA-29 (miR29) family is one of the most important regulatory pathways in cancer therapeutics. By targeting the suppressors of p53, a tumor suppressor protein, miR29 induces apoptosis of cancer cells through p53 stabilization. Here, we identify a novel synthesized amphiphilic peptide, LK-L1C/K6W/L8C, which enhances expression of miR29b and promotes p53 activity. In the presence of LK-L1C/K6W/L8C, pre-miR29b preferentially forms a complex with the Dicer protein through interaction of LK-L1C/K6W/L8C with the terminal loop region of pre-miR29b, leading to an increase in Dicer processing. Furthermore, LK-L1C/K6W/L8C stimulates apoptosis by improving p53 stability in miR29-inducible HeLa and MCF7 cells. Collectively, our study shows that a peptide can directly influence the miR29b-mediated p53 activation pathway in cancer cells. Therefore, our findings provide the basis for a new, potentially promising peptide-based drug for cancer therapy.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Igojo
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department of Chemistry and Education, Seoul National University, Seoul, Republic of Korea.
authors.forename: Soonsil
authors.initials: S
authors.lastname: Hyun
authors.affiliation: Department of Chemistry and Education, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Research Institute of Agriculture and Life Sciences, and Plant Genomics and Breeding Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Chanseok
authors.initials: C
authors.lastname: Shin