CAJ | 학술논문

miR－34a是一个非编码蛋白的单链小分子RNA，在转录水平上通过碱基配对3’－端非翻译区域抑制靶基因表达，多用于肿瘤学的研究中，可通过下调原癌基因的表达抑制肿瘤细胞生长，近年发现其参与骨代谢过程中骨稳态的调节。 Tgif2通过与DNA结合或与TGFβ激活的Smads相互作用抑制TGFβ基因表达而抑制成骨细胞的增殖，且Tgif2与RNAKL通路形成一个正反馈循环，RNAKL通路诱导的转录因子增加Tgif2活性，Tgif2又反过来促进RNAKL通路中转导因子的活性，从而促进破骨细胞的生长分化，miR－34a主要通过下调Tgif2基因的表达，促进成骨细胞增殖，且miR－34a下调Tgif2表达时，也间接抑制了OPG／RANK／RANKL通路的转导，抑制破骨细胞增殖、分化。同时MiR－34a是肿瘤抑制基因P53最常见的转录靶点，P53不仅在转录水平对miR－34a进行调节，而且影响miR－34a前体形成和成熟。 P53、miR－34a及Tgif2三者相互作用，直接影响成骨破骨细胞的增殖与分化，且与多个经典信号通路均有交叉，如OPG／RANK／RANKL 通路、 Wnt／β－catenin经典信号通路，参与经典通路中相关因子的调节，间接影响骨稳态。因此，研究miR－34a如何调节成骨破骨分化及协调细胞内其他调节通路共同维持骨稳态将会成为防治骨质疏松症的重要研究方向。
miR－34a시일개비편마단백적단련소분자RNA，재전록수평상통과감기배대3’－단비번역구역억제파기인표체，다용우종류학적연구중，가통과하조원암기인적표체억제종류세포생장，근년발현기삼여골대사과정중골은태적조절。 Tgif2통과여DNA결합혹여TGFβ격활적Smads상호작용억제TGFβ기인표체이억제성골세포적증식，차Tgif2여RNAKL통로형성일개정반궤순배，RNAKL통로유도적전록인자증가Tgif2활성，Tgif2우반과래촉진RNAKL통로중전도인자적활성，종이촉진파골세포적생장분화，miR－34a주요통과하조Tgif2기인적표체，촉진성골세포증식，차miR－34a하조Tgif2표체시，야간접억제료OPG／RANK／RANKL통로적전도，억제파골세포증식、분화。동시MiR－34a시종류억제기인P53최상견적전록파점，P53불부재전록수평대miR－34a진행조절，이차영향miR－34a전체형성화성숙。 P53、miR－34a급Tgif2삼자상호작용，직접영향성골파골세포적증식여분화，차여다개경전신호통로균유교차，여OPG／RANK／RANKL 통로、 Wnt／β－catenin경전신호통로，삼여경전통로중상관인자적조절，간접영향골은태。인차，연구miR－34a여하조절성골파골분화급협조세포내기타조절통로공동유지골은태장회성위방치골질소송증적중요연구방향。
miR-34a is a non-coding, single-stranded small RNA, which inhibits gene expression at the post-transcriptional level through nucleotide base pairing between complementary sequences of miRNAs and 3 ’-untranslated regions of messenger RNAs ( mRNAs ) .It has been demonstrated to function as a tumor suppressor by down-regulating the expression of many essential oncogenes and therefore it is often used in the studies of oncology.Recently it has been found to be involved in the regulation of bone homeostasis.Tgif2 has been reported to represses osteoblast proliferation by binding directly to DNA or interacts with TGFβ-activated Smads.Tgif2 intensifies osteoclastogenesis through a positive feedback loop in which RANKL-induced transcription factors activate Tgif2 expression, and Tgif2 in turn promotes their activity.MiR-34a facilitates osteogenesis by down-regulating Tgif2 expression and restrains osteoclastogenesis by indirectly suppressing OPG/RANK/RANKL signal pathway while down-regulating Tgif2.Meanwhile, miR-34a is a direct transcriptional target of the tumor suppressor p53 that mediates genetic transcription of miR-34a and their form of pre-miRNA.The interaction of miR-34a, Tgif2, and P53 regulates bone homeostasis directly through affecting proliferation and differentiation of osteoblasts and osteoclasts.The action indirectly affects bone homeostasis by involving many factors in the classical signal pathways and by crosslinking with OPG/RANK/RANKL and Wnt/β-catenin signal pathways. Therefore, it is meaningful to investigate how miR-34 regulates osteoblast and osteoclast differentiation and how it interacts with other signal pathways to modulate bone homeostasis.