iScience.2022 Feb 21;25(3):103949.doi: 10.1016/j.isci.2022.103949. eCollection 2022 Mar 18.

Long noncoding RNA Lnc-DIF inhibits bone formation by sequestering miR-489-3p

Chong Yin  1   2   3 Ye Tian  1 Dijie Li  1 Yang Yu  4 Shanfeng Jiang  1 Yimei Hou  3 Meng Deng  3 Kaiyuan Zheng  3 Yan Zhang  1 Xiaoni Deng  1 Zhihao Chen  1 Zhiping Miao  1 Qiang Hao  5 Yu Li  1 Airong Qian  1 Affiliations

Free PMC article

Abstract

Osteoporosis has become a high incident bone disease along with the aging of human population. Long noncoding RNAs (LncRNAs) play an important role in osteoporosis incidence. In this study, we screened out an LncRNA negatively correlated with osteoblast differentiation, which was therefore named Lnc-DIF (differentiation inhibiting factor). Functional analysis proved that Lnc-DIF inhibited bone formation. A special structure containing multiple 53 nucleotide repeats was found in the trailing end of Lnc-DIF. Our study suggested that this repeat sequence could sequester multiple miR-489-3p and inhibit bone formation through miR-489-3p/SMAD2 axis. Moreover, siRNA of Lnc-DIF would rescue bone formation in both aging and ovariectomized osteoporosis mice. This study revealed a kind of LncRNA that could function as a sponge and regulate multiple miRNAs. RNA therapy techniques that target these LncRNAs could manipulate its downstream miRNA-target pathway with significantly higher efficiency and specificity. This provided potential therapeutic insight for RNA-based therapy for osteoporosis.

Keywords: Biological sciences; Molecular biology; Molecular mechanism of gene regulation; Orthopedics.

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