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Silencing long noncoding RNA colon cancer-associated transcript-1 upregulates microRNA-34a-5p to promote proliferation and differentiation of osteoblasts in osteoporosis

Cancer Gene Therapy volume 28, pages 1150–1161 (2021)Cite this article

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Abstract

Long noncoding RNAs (lncRNAs) have been revealed to be related to multiple physiological and pathology processes such as development, carcinogenesis, and osteogenesis. It is reported that lncRNAs might exert function in osteoblast differentiation and bone formation. Here, we determined this study to clarify whether lncRNA CCAT1 could regulate osteoblast proliferation and differentiation in ovariectomized rats with osteoporosis. The osteoporosis models were established by bilateral ovariectomy and treated with CCAT1 siRNAs to discuss the effect of CCAT1 on pathological changes and osteocyte apoptosis in ovariectomized rats with osteoporosis. The osteoblasts from ovariectomized rats were cultured in vitro, which were then treated with CCAT1 siRNAs to explore the role of CCAT1 in osteoblast proliferation and differentiation. Moreover, the relationships among CCAT1, miR-34a-5p, and SMURF2 were confirmed. CCAT1 and SMURF2 were amplified while miR-34a-5p expression was inhibited in bone tissues and osteoblasts of ovariectomized rats with osteoporosis. Inhibited CCAT1 improved pathology and restricted osteocyte apoptosis of bone tissues in ovariectomized rats with osteoporosis in vivo, and also enhanced differentiation, mineralization abilities, and proliferation, and suppressed apoptosis of osteoblasts from ovariectomized rats in vitro through upregulating miR-34a-5p expression. LncRNA CCAT1 could competitively bind with miR-34a-5p to prevent the degradation of its target gene SMURF2. Results of this research suggested that the CCAT1 inhibits the proliferation and differentiation of osteoblasts in rats with osteoporosis by binding to miR-34a-5p, providing novel biomarkers for osteoporosis treatment.

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Fig. 1: Results of serological, visceral organ wet weight and TRACP staining.
Fig. 2: Inhibited CCAT1 or elevated miR-34a-5p improve pathology in bone tissues of ovariectomized rats with osteoporosis.
Fig. 3: Inhibited CCAT1 or elevated miR-34a-5p promote expression of OPG, while restrain expression of SMURF2, RANK and RANKL in bone tissues of ovariectomized rats with osteoporosis.
Fig. 4: Inhibited CCAT1 or elevated miR-34a-5p enhance differentiation and mineralization abilities of osteoblasts from ovariectomized rats.
Fig. 5: Inhibited CCAT1 or elevated miR-34a-5p promote proliferation and inhibit apoptosis of osteoblasts from ovariectomized rats.
Fig. 6: CCAT1 negatively regulates miR-34a-5p and SMURF2 is the target gene of miR-34a-5p.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

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  1. These authors contributed equally: Fangke Hu, Chengying Jiang

Authors and Affiliations

  1. Department of Orthopedics, Tianjin Hospital, Tianjin, 300211, China

    Fangke Hu & Guoyun Bu

  2. Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

    Chengying Jiang & Yiru Fu

  3. Department of Endocrinology, The First People’s Hospital of Yunnan Province, Kunming, 650032, China

    Yanfang Yu

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  1. Fangke Hu
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Correspondence to Yanfang Yu.

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Animal experiments were strictly in accordance with the Guide to the Management and Use of Laboratory Animals issued by the National Institutes of Health. The protocol of animal experiments was approved by the Institutional Animal Care and Use Committee of the First People’s Hospital of Yunnan Province.

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Hu, F., Jiang, C., Bu, G. et al. Silencing long noncoding RNA colon cancer-associated transcript-1 upregulates microRNA-34a-5p to promote proliferation and differentiation of osteoblasts in osteoporosis. Cancer Gene Ther 28, 1150–1161 (2021). https://doi.org/10.1038/s41417-020-00264-7

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