title: Down-regulation of Phospholipase D Stimulates Death of Lung Cancer Cells Involving Up-regulation of the Long ncRNA ANRIL.
abstract: Dysregulation of phospholipase D (PLD) has been found in several types of human cancer, but the underlying regulatory mechanism remains poorly-understood. Herein we found PLD inhibition in human H460 lung cancer cells has anti-tumorigenic effects such as stimulation of apoptosis and autophagy. In the present study, in order to identify the responsible key regulator of these anti-tumorigenic effects of PLD inhibition, we analyzed the expression levels of 90 long non-coding RNAs (lncRNAs). Among them, the expression level of antisense noncoding RNA in the INK4 locus (ANRIL) was increased up to 13.6-fold by PLD inhibition in H460 human lung cancer cells. Moreover, knockdown of ANRIL using its specific small-interfering RNA significantly suppressed PLD inhibition-induced apoptosis. Collectively, our findings showed that ANRIL is an lncRNA responsible in anti-tumorigenesis caused by PLD inhibition and combined incorporation of ANRIL into PLD inhibition-induced anti-tumorigenic signaling network could be a new effective therapeutic approach for controlling lung cancer.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Yeon-Ho
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Republic of Korea.
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Republic of Korea jineunjung@wku.ac.kr.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding; D010739:Phospholipase D
keywords: ANRIL; H460 cells; LncRNA; PLD inhibitor; lung cancer