Sato Akira, Omi Takuya, Yamamoto Akihiro, Satake Akito, Hiramoto Akiko, Masutani Mitsuko, Tanuma Sei-ichi, Wataya Yusuke, Kim Hye-Sook
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda, Chiba, Japan.
Division of Genome Stability Research, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
PLoS One. 2016 Apr 12;11(4):e0153130. doi: 10.1371/journal.pone.0153130. eCollection 2016.
Cell-death can be necrosis and apoptosis. We are investigating the mechanisms regulating the cell death that occurs on treatment of mouse cancer cell-line FM3A with antitumor 5-fluoro-2'-deoxyuridine (FUdR): necrosis occurs for the original clone F28-7, and apoptosis for its variant F28-7-A. Here we report that a microRNA (miR-351) regulates the cell death pattern. The miR-351 is expressed strongly in F28-7-A but only weakly in F28-7. Induction of a higher expression of miR-351 in F28-7 by transfecting an miRNA mimic into F28-7 resulted in a change of the death mode; necrosis to apoptosis. Furthermore, transfection of an miR-351 inhibitor into F28-7-A resulted in the morphology change, apoptosis to necrosis, in this death-by-FUdR. Possible mechanism involving lamin B1 in this miR-351's regulatory action is discussed.
细胞死亡可分为坏死和凋亡。我们正在研究用抗肿瘤药物5-氟-2'-脱氧尿苷(FUdR)处理小鼠癌细胞系FM3A时发生的细胞死亡的调控机制:原始克隆F28-7发生坏死,而其变体F28-7-A发生凋亡。在此我们报告一种微小RNA(miR-351)调控细胞死亡模式。miR-351在F28-7-A中强烈表达,但在F28-7中仅微弱表达。通过将miRNA模拟物转染到F28-7中诱导F28-7中miR-351更高表达,导致死亡模式改变;从坏死转变为凋亡。此外,将miR-351抑制剂转染到F28-7-A中导致在这种由FUdR引起的死亡中形态学改变,从凋亡转变为坏死。本文讨论了在这种miR-351的调控作用中涉及核纤层蛋白B1的可能机制。