Takaki Akamine1,2, Yosuke Morodomi1,2, Yui Harada2, Koji Teraishi1,2, Tetsuzo Tagawa1, Tatsuro Okamoto1, Yoshihiko Maehara1, Yoshikazu Yonemitsu3. 1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. 3. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan yonemitu@med.kyushu-u.ac.jp.
Abstract
BACKGROUND/AIM: Alterations of microRNA expression in three-dimensional spheroids were examined to identify novel microRNAs that might be associated with tumorigenesis. MATERIALS AND METHODS: Using microRNA microarray analysis, we screened for microRNAs that were dramatically up-regulated inside three-dimensional spheroids in genetically-modified HCT116 human colon cancer cells expressing Copepoda Green Fluorescent Protein under hypoxia. RESULTS: miR-3148 was identified as a possible candidate onco-microRNA. A growth advantage of HCT116 cells stably expressing miR-3148 (HCT116-miR3148) was observed compared to parental cells in vivo, but not in vitro. Additionally, no change in growth under hypoxic or starvation conditions was seen in these cells cultured two-dimensionally; however, HCT116-miR3148 cells maintained as three-dimensional spheroids were highly resistant to hypoxic conditions. HCT116-miR3148 cells were more sensitive to mitogen-activated protein kinase (MAPK) kinase inhibitors and extracellular signal-regulated kinase (ERK) inhibitors. CONCLUSION: MiR-3148 may be a novel onco-microRNA that protects cancer cells from serious stress conditions through the MAPK/ERK pathway, especially in vivo. Copyright
BACKGROUND/AIM: Alterations of microRNA expression in three-dimensional spheroids were examined to identify novel microRNAs that might be associated with tumorigenesis. MATERIALS AND METHODS: Using microRNA microarray analysis, we screened for microRNAs that were dramatically up-regulated inside three-dimensional spheroids in genetically-modified HCT116 humancolon cancer cells expressing Copepoda Green Fluorescent Protein under hypoxia. RESULTS:miR-3148 was identified as a possible candidate onco-microRNA. A growth advantage of HCT116 cells stably expressing miR-3148 (HCT116-miR3148) was observed compared to parental cells in vivo, but not in vitro. Additionally, no change in growth under hypoxic or starvation conditions was seen in these cells cultured two-dimensionally; however, HCT116-miR3148 cells maintained as three-dimensional spheroids were highly resistant to hypoxic conditions. HCT116-miR3148 cells were more sensitive to mitogen-activated protein kinase (MAPK) kinase inhibitors and extracellular signal-regulated kinase (ERK) inhibitors. CONCLUSION:MiR-3148 may be a novel onco-microRNA that protects cancer cells from serious stress conditions through the MAPK/ERK pathway, especially in vivo. Copyright
Authors: Radhakrishnan Vishnubalaji; Ramesh Elango; Muthurangan Manikandan; Abdul-Aziz Siyal; Dalia Ali; Ammar Al-Rikabi; Dana Hamam; Rimi Hamam; Hicham Benabdelkamel; Afshan Masood; Ibrahim O Alanazi; Assim A Alfadda; Musaad Alfayez; Abdullah Aldahmash; Moustapha Kassem; Nehad M Alajez Journal: Cell Death Discov Date: 2020-09-01