LRRC4 mediates the formation of circular RNA CD44 to inhibitGBM cell proliferation.
LRRC4 mediates the formation of circular RNA CD44 to inhibitGBM cell proliferation.
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DOI：
10.1016/j.omtn.2021.08.026
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发表时间：
2021-12-03
期刊：
影响因子：
--
通讯作者：
Wu M
中科院分区：
文献类型：
--
作者：
Feng J;Ren X;Fu H;Li D;Chen X;Zu X;Liu Q;Wu M
越来越多的证据表明，环状RNA（circRNA）的失调参与胶质母细胞瘤的发展。富含亮氨酸的重复序列4（LRRC 4）已被证明可以抑制胶质母细胞瘤中的肿瘤。然而，LRRC 4是否可以调节circRNA的形成尚不清楚。在这项研究中，LRRC 4被发现与SAM 68相互作用。LRRC 4通过抑制SAM 68与CD 44前体mRNA的结合促进circCD 44的生成。此外，在多形性胶质母细胞瘤（GBM）组织和GBM原代细胞中发现了circCD 44的表达下调。circCD 44的再表达显著抑制GBM细胞的增殖、集落形成和侵袭，并抑制体内肿瘤生长。在机制上，circCD 44可以通过海绵状吸收参与GBM进展的miR-326和miR-330- 5 p来调节SMAD 6的表达。因此，LRRC 4/SAM 68/circCD 44/miR-326/miR-330- 5 p/SMAD 6信号传导轴可能是GBM治疗的潜在靶标。研究表明，富含亮氨酸重复序列的4通过抑制SAM 68与CD 44前体mRNA的结合促进新型抑制性circCD 44的产生，通过SAM 68/circCD 44/miR-326/miR-330- 5 p/SMAD 6信号传导轴抑制多形性胶质母细胞瘤细胞增殖，因此为胶质母细胞瘤提供了潜在的治疗靶点。
Mounting evidence reveals that dysregulation of circular RNAs (circRNAs) is involved in the development of glioblastoma. Leucine-rich repeat-containing 4 (LRRC4) has been shown to suppress tumors in glioblastoma. However, whether LRRC4 can regulate the formation of circRNA is not yet understood. In this study, LRRC4 was found to interact with SAM68. LRRC4 promoted the generation of circCD44 by inhibiting the binding between SAM68 and CD44 pre-mRNA. Moreover, downregulated expression of circCD44 was found in glioblastoma multiforme (GBM) tissues and GBM primary cells. Re-expression of circCD44 significantly suppressed the proliferation, colony formation, and invasion of GBM cells and inhibited tumor growth in vivo. Mechanistically, circCD44 could regulate the expression of SMAD6 via sponging miR-326 and miR-330-5p involved in the progression of GBM. Thus, the LRRC4/SAM68/circCD44/miR-326/miR-330-5p/SMAD6 signaling axis could be a potential target for GBM treatment. Studies demonstrate that leucine-rich repeat-containing 4 promotes the generation of a novel suppressive circCD44 by restraining the binding between SAM68 and CD44 pre-mRNA, inhibits glioblastoma multiforme cell proliferation through the SAM68/circCD44/miR-326/miR-330-5p/SMAD6 signaling axis, and therefore provides a potential therapeutic target for glioblastoma.
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含有 4 的富含亮氨酸重复序列可作为自噬抑制剂，恢复胶质母细胞瘤对替莫唑胺的敏感性
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