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PRPF4 is a novel therapeutic target for the treatment of breast cancer by influencing growth, migration, invasion, and apoptosis of breast cancer cells via p38 MAPK signaling pathway.
Park, Song; Han, Se-Hyeon; Kim, Hyeon-Gyeom; Jeong, Jain; Choi, Minjee; Kim, Hee-Yeon; Kim, Min-Gi; Park, Jin-Kyu; Han, Jee Eun; Cho, Gil-Jae; Kim, Myoung Ok; Ryoo, Zae Young; Choi, Seong-Kyoon.
Afiliación
  • Park S; Core Protein Resources Center, DGIST, Daegu, Republic of Korea.
  • Han SH; Department of News-team, SBS(Seoul Broadcasting Station), Mokdongseo-ro 161, Yangchungu, Seoul, South Korea; School of Media Communication, Hanyang University, Wangsibri-ro 222, Seongdonggu, Seoul, South Korea.
  • Kim HG; Core Protein Resources Center, DGIST, Daegu, Republic of Korea; School of Life Science, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, South Korea.
  • Jeong J; Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
  • Choi M; Core Protein Resources Center, DGIST, Daegu, Republic of Korea; School of Life Science, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, South Korea.
  • Kim HY; Core Protein Resources Center, DGIST, Daegu, Republic of Korea.
  • Kim MG; Core Protein Resources Center, DGIST, Daegu, Republic of Korea.
  • Park JK; College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, South Korea.
  • Han JE; College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, South Korea.
  • Cho GJ; College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, South Korea.
  • Kim MO; Department of Animal Science, College of Ecology and Environment Science, Kyungpook National University, Sangju, South Korea.
  • Ryoo ZY; School of Life Science, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, South Korea. Electronic address: jaewoong64@hanmail.net.
  • Choi SK; Core Protein Resources Center, DGIST, Daegu, Republic of Korea; Division of Biotechnology, DGIST, Daegu, Republic of Korea. Electronic address: cskbest@dgist.ac.kr.
Mol Cell Probes ; 47: 101440, 2019 10.
Article en En | MEDLINE | ID: mdl-31445970
Pre-mRNA processing factor 4 (PRPF4), a core protein in U4/U6 snRNP, maintains snRNP structures by interacting with PRPF3 and cyclophilin H. Expression of the PRPF4 gene affects cell survival as well as apoptosis and is responsible for retinitis pigmentosa (RP). Proteomics analysis shows that PRPF4 may be a therapeutic target in human cancers. Nevertheless, the exact function and role of the PRPF4 gene are unclear. In this study, we assessed the expression of PRPF4 gene in human breast cancer cells. First, we confirmed that the PRPF4 gene was overexpressed in various breast cancer cell lines. Next, using breast cancer cell lines MCF7 and MDA-MB-468, we established stable cell lines with PRPF4 gene knockdown. We also performed microarray analysis to investigate molecular mechanisms underlying PRPF4 activity. All cell lines with PRPF4 gene knockdown exhibited reduced cell proliferation, remarkable reduction in anchorage-independent colony formation capacity, and reduction of PCNA protein, which is a marker cell of proliferation. Reduced expression of the PRPF4 gene induced apoptosis and changes in the expression of associated apoptotic markers in breast cancer cell lines. Knockdown of the PRPF4 gene reduced cellular capacity for migration and invasion (the key hallmarks of human cancers) and decreased the expression of genes involved in epithelial-mesenchymal transition (EMT). Microarray results showed that the expression of PPIP5K1, PPIPK2, and YWHAE genes was reduced at the transcriptional level, leading to reduced phosphorylation of p38 MAPK. These findings suggest that knockdown of PRPF4 gene slows down breast cancer progression via suppression of p38 MAPK phosphorylation. In conclusion, the PRPF4 gene plays an important role in the growth of breast cancer cells and is therefore a potential therapeutic target.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación hacia Arriba / Ribonucleoproteína Nuclear Pequeña U4-U6 / Proteínas Quinasas p38 Activadas por Mitógenos Límite: Female / Humans Idioma: En Revista: Mol Cell Probes Asunto de la revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Regulación hacia Arriba / Ribonucleoproteína Nuclear Pequeña U4-U6 / Proteínas Quinasas p38 Activadas por Mitógenos Límite: Female / Humans Idioma: En Revista: Mol Cell Probes Asunto de la revista: BIOLOGIA MOLECULAR / BIOTECNOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido