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Fig.1:Model for the regulation of osteoclastogenesis by the Malat1-Tead3-Nfatc1 axis.DOI:https://doi.org/10.1038/s41467-024-46602-3


MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. Zhao et al. found that Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, Malat1 binds to Tead3 protein, a macrophage-osteoclast-specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis, which results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation.

Besides, Wang et al. found that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. It was determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. KCNQ1OT1 stifled the miR-421-3p expression which can bind the mTOR. In all, KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis.

  1. Zhao Y, Ning J, Teng H, Deng Y, Sheldon M, Shi L, Martinez C, Zhang J, Tian A, Sun Y, Nakagawa S, Yao F, Wang H, Ma L. Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis. Nat Commun. 2024 Mar 16;15(1):2384.

  2. Wang Z, Zhang H, Li Q, Zhang L, Chen L, Wang H, Chen Y. Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis. Sci Rep. 2023 Feb 9;13(1):2333.