Cancer-associated fibroblast-derived exosomal LINC00930 represses cell malignancy and glycolysis by recruiting MBNL1 and elevating PRKAA2 stability in colorectal cancer.

IF 4.8 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Chunhui Cui, Lifeng Wang, Jinlong Yu, Changhui Yu, Huiyan Zhang
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引用次数: 0

Abstract

Exosomes (EXOs) secreted by cancer-associated fibroblasts (CAFs) can induce malignant phenotypes of tumor cells. The long non-coding RNA LINC00930 is known for promoting cancer cell glycolysis and proliferation. However, its role and mechanism in colorectal cancer (CRC) are unclear. This study aimed to determine whether CAF-derived exosomal LINC00930 is involved in CRC progression. In our study, LINC00930 was significantly downregulated in CRC samples and cell lines, as well as in CAFs and CAF-derived EXOs. Functionally, CAF-derived exosomal LINC00930 inhibited CRC cell proliferation, migration, invasion, and glycolysis in vitro and impaired tumor growth in patient-derived xenograft models. LINC00930 improved PRKAA2 stability by recruiting MBNL1. Furthermore, PRKAA2 silencing partly reversed CAF-derived exosomal LINC00930-mediated effects on CRC cell proliferation, migration, invasion, and glycolysis. In conclusion, this study identifies LINC00930 as a tumor-suppressive lncRNA delivered by CAF-derived EXOs that inhibits CRC progression through the MBNL1-PRKAA2 axis, suggesting that LINC00930 could be a viable therapeutic target for CRC.

癌症相关成纤维细胞来源的外泌体LINC00930通过募集MBNL1和提高PRKAA2的稳定性来抑制结直肠癌中的细胞恶性和糖酵解。
由癌相关成纤维细胞(CAFs)分泌的外泌体(EXOs)可诱导肿瘤细胞的恶性表型。长链非编码RNA LINC00930以促进癌细胞糖酵解和增殖而闻名。然而,其在结直肠癌(CRC)中的作用和机制尚不清楚。本研究旨在确定caf来源的外泌体LINC00930是否参与结直肠癌的进展。在我们的研究中,LINC00930在CRC样本和细胞系以及CAFs和CAFs衍生的exo中显著下调。在功能上,caf来源的外泌体LINC00930在体外抑制结直肠癌细胞的增殖、迁移、侵袭和糖酵解,并在患者来源的异种移植模型中损害肿瘤生长。LINC00930通过募集MBNL1改善了PRKAA2的稳定性。此外,PRKAA2沉默部分逆转了caf来源的外泌体linc00930介导的结直肠癌细胞增殖、迁移、侵袭和糖酵解的作用。总之,本研究确定了LINC00930是一种由caf衍生的exo传递的肿瘤抑制lncRNA,通过MBNL1-PRKAA2轴抑制CRC的进展,这表明LINC00930可能是CRC的可行治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
European Journal of Medical Research
European Journal of Medical Research 医学-医学:研究与实验
CiteScore
3.20
自引率
0.00%
发文量
247
审稿时长
>12 weeks
期刊介绍: European Journal of Medical Research publishes translational and clinical research of international interest across all medical disciplines, enabling clinicians and other researchers to learn about developments and innovations within these disciplines and across the boundaries between disciplines. The journal publishes high quality research and reviews and aims to ensure that the results of all well-conducted research are published, regardless of their outcome.
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