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OIP5-AS1 对 miRNAs 的选择性海绵作用调控了人结直肠癌细胞腺-癌转化中丙酮酸的代谢重编程。

The selective sponging of miRNAs by OIP5-AS1 regulates metabolic reprogramming of pyruvate in adenoma-carcinoma transition of human colorectal cancer.

机构信息

Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, 314001, China.

School of Medicine, Jiaxing University, No 118, Road Jiahang Avenue, Jiaxing, Zhejiang, 314001, China.

出版信息

BMC Cancer. 2024 May 21;24(1):611. doi: 10.1186/s12885-024-12367-7.

DOI:10.1186/s12885-024-12367-7
PMID:38773399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11106987/
Abstract

RNA interactomes and their diversified functionalities have recently benefited from critical methodological advances leading to a paradigm shift from a conventional conception on the regulatory roles of RNA in pathogenesis. However, the dynamic RNA interactomes in adenoma-carcinoma sequence of human CRC remain unexplored. The coexistence of adenoma, cancer, and normal tissues in colorectal cancer (CRC) patients provides an appropriate model to address this issue. Here, we adopted an RNA in situ conformation sequencing technology for mapping RNA-RNA interactions in CRC patients. We observed large-scale paired RNA counts and identified some unique RNA complexes including multiple partners RNAs, single partner RNAs, non-overlapping single partner RNAs. We focused on the antisense RNA OIP5-AS1 and found that OIP5-AS1 could sponge different miRNA to regulate the production of metabolites including pyruvate, alanine and lactic acid. Our findings provide novel perspectives in CRC pathogenesis and suggest metabolic reprogramming of pyruvate for the early diagnosis and treatment of CRC.

摘要

RNA 相互作用组及其多样化的功能最近受益于关键方法学的进步,这导致了 RNA 在发病机制中的调控作用的传统观念发生了转变。然而,人类 CRC 的腺瘤-癌序列中的动态 RNA 相互作用组仍未被探索。结直肠癌 (CRC) 患者中腺瘤、癌症和正常组织的共存为解决这一问题提供了一个合适的模型。在这里,我们采用 RNA 原位构象测序技术来绘制 CRC 患者的 RNA-RNA 相互作用图谱。我们观察到大规模的配对 RNA 计数,并鉴定出一些独特的 RNA 复合物,包括多个伴侣 RNA、单个伴侣 RNA、非重叠的单个伴侣 RNA。我们专注于反义 RNA OIP5-AS1,并发现 OIP5-AS1 可以吸附不同的 miRNA 来调节包括丙酮酸、丙氨酸和乳酸在内的代谢物的产生。我们的发现为 CRC 的发病机制提供了新的视角,并为 CRC 的早期诊断和治疗提供了丙酮酸代谢重编程的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/f8d3ceead679/12885_2024_12367_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/c7dffe66c158/12885_2024_12367_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/f8d3ceead679/12885_2024_12367_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/8550c833dcc9/12885_2024_12367_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/3568ad781b91/12885_2024_12367_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/1b540f242dba/12885_2024_12367_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/063b32e8953f/12885_2024_12367_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/c7dffe66c158/12885_2024_12367_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/162c/11106987/f8d3ceead679/12885_2024_12367_Fig7_HTML.jpg

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