Functions and mechanisms of circular RNAs in regulating stem cell differentiation

Lin, Zhengjun; Tang, Xianzhe; Wan, Jia; Zhang, Xianghong; Liu, Chunfeng; Liu, Tang

doi:10.1080/15476286.2021.1913551

Cited by 41 publications

(19 citation statements)

References 111 publications

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“…In humans, osteoblasts, which are involved in bone formation, are inseparable from the differentiation of bone marrow mesenchymal stem cells. Studies have shown that circRNAs play an important role in the osteogenic differentiation of BMSCs, and different circRNAs can either promote or inhibit the osteogenic differentiation of BMSCs ( 41 ). Fu et al ( 42 ) found differentially expressed circRNAs in patients with osteoporosis (OP), and the study identified 237 upregulated and 279 downregulated circRNAs, which also confirmed that the role of circRNAs in the osteogenic differentiation of BMSCs is important in the process.…”

Section: Associations Between Circrnas and Bmscsmentioning

confidence: 99%

Roles of circular RNAs in osteogenic differentiation of bone marrow mesenchymal stem cells (Review)

Wang

Zhang

et al. 2022

Mol Med Rep

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Bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts, chondrocytes, adipocytes and even myoblasts, and are therefore defined as pluripotent cells. BMSCs have become extremely important seed cells in gene therapy, tissue engineering, cell replacement therapy and regenerative medicine due to their potential in multilineage differentiation, self-renewal, immune regulation and other fields. Circular RNAs (circRNAs) are a class of non-coding RNAs that are widely present in eukaryotic cells. Unlike standard linear RNAs, circRNAs form covalently closed continuous loops with no 5′ or 3′ polarity. circRNAs are abundantly expressed in cells and tissues, and are highly conserved and relatively stable during evolution. Numerous studies have shown that circRNAs play an important role in the osteogenic differentiation of BMSCs. Further studies on the role of circRNAs in the osteogenic differentiation of BMSCs can provide a new theoretical and experimental basis for bone tissue engineering and clinical treatment.

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Section: Associations Between Circrnas and Bmscsmentioning

confidence: 99%

Roles of circular RNAs in osteogenic differentiation of bone marrow mesenchymal stem cells (Review)

Wang

Zhang

et al. 2022

Mol Med Rep

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“…CircRNAs are a novel class of non-coding RNAs, which are involved in various physiological and pathological processes (43). They exhibit a clear regulatory function in the proliferation and migration of various tumor cells.…”

Section: Discussionmentioning

confidence: 99%

CircRNA-mediated regulation of brown adipose tissue adipogenesis

Liu

Deng

et al. 2022

Front. Nutr.

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Adipose tissue represents a candidate target for the treatment of metabolic illnesses, such as obesity. Brown adipose tissue (BAT), an important heat source within the body, promotes metabolic health through fat consumption. Therefore, the induction of white fat browning may improve lipid metabolism. Currently, the specific roles of circRNA in BAT and white adipose tissue (WAT) remain elusive. Herein, we conducted circRNA expression profiling of mouse BAT and WAT using RNA-seq. We identified a total of 12,183 circRNAs, including 165 upregulated and 79 downregulated circRNAs between BAT and WAT. Differentially expressed (DE) circRNAs were associated with the mitochondrion, mitochondrial part, mitochondrial inner membrane, mitochondrial envelope, therefore, these circRNAs may affect the thermogenesis and lipid metabolism of BAT. Moreover, DE circRNAs were enriched in browning- and thermogenesis-related pathways, including AMPK and HIF-1 signaling. In addition, a novel circRNA, circOgdh, was found to be highly expressed in BAT, formed by back-splicing of the third and fourth exons of the Ogdh gene, and exhibited higher stability than linear Ogdh. circOgdh was mainly distributed in the cytoplasm and could sponge miR-34a-5p, upregulating the expression of Atgl, a key lipolysis gene, which enhanced brown adipocyte lipolysis and suppressed lipid droplet accumulation. Our findings offer in-depth knowledge of the modulatory functions of circRNAs in BAT adipogenesis.

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“…Now, research articles about the relationship of hucMSC treatment and circRNA are rare. In several articles, only the regulation of circRNA on hucMSC differentiation, not hucMSC treatment, is discussed [32][33][34][35]. The role and mechanism of circRNA in hucMSC treatment have not been reported.…”

Section: Discussionmentioning

confidence: 99%

hucMSC treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis

Zhang

et al. 2022

Preprint

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Background Currently, no effective treatment has been developed for pulmonary fibrosis. This study was performed to determine the effect of human umbilical cord mesenchymal stem cell (hucMSC) treatment on pulmonary fibrosis and investigate the circFOXP1-mediated mechanism of hucMSC treatment on autophagy. Methods Pulmonary fibrosis models were established by spraying bleomycin in mice and TGF-β1 treatment of MRC-5 cell. The effect of hucMSC treatment was investigated using morphological and functional experiments. The mechanism of hucMSC treatment in pulmonary fibrosis was explored by gain- and loss-of-function studies and rescue experiments. Results Results showed that hucMSC treatment alleviated pulmonary fibrosis. Morphological staining indicated that hucMSC-treated mice had thinner alveolar wall, effectively improved alveolar structure, significantly reduced alveolar inflammation, and decreased collagen deposition than control mice. Fibrotic proteins, including vimentin, α-SMA, collagen I, and collagen III, and the differentiation-related protein S100 calcium binding protein A4 were reduced considerably in the hucMSC-treated group. The mechanistic study revealed that the inhibition of hucMSC treatment on pulmonary fibrogenesis depended on downregulating circFOXP1, in which hucMSC treatment promoted circFOXP1-mediated autophagy process via blocking the nuclear HuR translocation and promoting the HuR degradation, leading to a marked decrease in autophagy negative regulators EZH2, STAT1 and FOXK1. Conclusion hucMSC treatment significantly improved pulmonary fibrosis by downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis. hucMSCs can act as an effective treatment for pulmonary fibrosis.

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Functions and mechanisms of circular RNAs in regulating stem cell differentiation

Cited by 41 publications

References 111 publications

Roles of circular RNAs in osteogenic differentiation of bone marrow mesenchymal stem cells (Review)

Roles of circular RNAs in osteogenic differentiation of bone marrow mesenchymal stem cells (Review)

CircRNA-mediated regulation of brown adipose tissue adipogenesis

hucMSC treatment ameliorated pulmonary fibrosis via downregulating the circFOXP1–HuR–EZH2/STAT1/FOXK1 autophagic axis

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