Human Endogenous Retrovirus (HERV)-K env Gene Knockout Affects Tumorigenic Characteristics of nupr1 Gene in DLD-1 Colorectal Cancer Cells

International Journal of Molecular Sciences

Kyudong Han¹  Juan L. Iovanna²  Yung Hyun Choi³  Heui-Soo Kim⁴  Seyoung Mun⁵  Eun-Ji Ko⁶  Hee-Jae Cha⁶  Mee Sun Ock⁶ 

[1] Center for BioMedical Engineering Core Facility, Dankook University, Cheonan 31116, Korea;Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, 13288 Marseille, France;Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 47227, Korea;Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, Korea;Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Korea;Departments of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Korea;

关键词: HERV-K Env;    colorectal cancer;    CRISPR-Cas9;    ROS;    NUPR1;    tumor suppressor;   

DOI  :  10.3390/ijms22083941

来源: DOAJ

【 摘 要 】

Human endogenous retroviruses (HERVs) are suggested to be involved in the development of certain diseases, especially cancers. To elucidate the function of HERV-K Env protein in cancers, an HERV-K env gene knockout (KO) in DLD-1 colorectal cancer cell lines was generated using the CRISPR-Cas9 system. Transcriptome analysis of HERV-K env KO cells using next-generation sequencing (NGS) was performed to identify the key genes associated with the function of HERV-K Env protein. The proliferation of HERV-K env KO cells was significantly reduced in in vitro culture as well as in in vivo nude mouse model. Tumorigenic characteristics, including migration, invasion, and tumor colonization, were also significantly reduced in HERV-K env KO cells. Whereas, they were enhanced in HERV-K env over-expressing DLD-1 cells. The expression of nuclear protein-1 (NUPR1), an ER-stress response factor that plays an important role in cell proliferation, migration, and reactive oxygen species (ROS) generation in cancer cells, significantly reduced in HERV-K env KO cells. ROS levels and ROS-related gene expression was also significantly reduced in HERV-K env KO cells. Cells transfected with NUPR1 siRNA (small interfering RNA) exhibited the same phenotype as HERV-K env KO cells. These results suggest that the HERV-K env gene affects tumorigenic characteristics, including cell proliferation, migration, and tumor colonization through NUPR1 related pathway.

【 授权许可】

Unknown