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长链非编码 RNA NORAD 通过海绵吸附 miR-577 来增强 TPM4,从而促进口腔鳞状细胞癌的进展。

LncRNA NORAD facilitates oral squamous cell carcinoma progression by sponging miR-577 to enhance TPM4.

机构信息

Department of Oral Implantology, Affiliated Hospital of Chifeng University, No. 4, Section 3, East Yuanlin Road, Chifeng, 024000, Inner Mongolia, China.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Chifeng University, Chifeng, 024000, Inner Mongolia, China.

出版信息

Biol Direct. 2022 Jan 6;17(1):1. doi: 10.1186/s13062-021-00299-2.

DOI:10.1186/s13062-021-00299-2
PMID:34991683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8734353/
Abstract

BACKGROUND

Long non-coding RNAs (lncRNAs) have been reported to be vital factors to affect the expression of genes and proteins. Also, it has been proved that the abnormal expression or mutation of lncRNAs stands as a signal of metastasis and proliferation of cancer. Nevertheless, the majority of lncRNAs still need to be explored in abundant cancers especially in oral squamous cell carcinoma (OSCC).

METHODS

RT-qPCR assays were applied to test the expression of RNAs. Mechanism assays were performed to verify the combination among NORAD, TPM4 and miR-577. Also, functional assays were conducted to verify the function of RNAs on OSCC cells.

RESULTS

LncRNA NORAD was highly expressed in OSCC tissues and cells. NORAD silencing repressed the biological behaviors of OSCC cells. MiR-577 was found in OSCC with low expression, and RIP assays illustrated that NORAD, miR-577 and TPM4 coexisted in RNA-induced silencing complexes. Rescue assays proved that the overexpression of TPM4 could recover the effect of NORAD silencing on OSCC progression.

CONCLUSIONS

It was revealed that NORAD functioned as a tumor promoter to sponge miR-577 thus elevating TPM4 in OSCC, which indicated that NORAD was worthy to be studied as a target for the treatment of OSCC.

摘要

背景

长链非编码 RNA(lncRNA)已被证明是影响基因和蛋白质表达的重要因素。此外,lncRNA 的异常表达或突变被认为是癌症转移和增殖的信号。然而,大多数 lncRNA 仍需要在丰富的癌症中进行探索,尤其是在口腔鳞状细胞癌(OSCC)中。

方法

采用 RT-qPCR 检测 RNA 的表达。通过机制实验验证 NORAD、TPM4 和 miR-577 之间的结合。此外,还进行了功能实验以验证 RNA 对 OSCC 细胞的功能。

结果

lncRNA NORAD 在 OSCC 组织和细胞中高表达。NORAD 沉默抑制了 OSCC 细胞的生物学行为。在 OSCC 中发现 miR-577 低表达,RIP 实验表明 NORAD、miR-577 和 TPM4 共同存在于 RNA 诱导的沉默复合物中。挽救实验证明,TPM4 的过表达可以恢复 NORAD 沉默对 OSCC 进展的影响。

结论

揭示了 NORAD 在 OSCC 中作为肿瘤促进子通过海绵吸附 miR-577 从而上调 TPM4 的功能,表明 NORAD 值得作为治疗 OSCC 的靶点进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/4927984024bc/13062_2021_299_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/af785aa76464/13062_2021_299_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/4f32f41f524a/13062_2021_299_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/f8530d652306/13062_2021_299_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/4927984024bc/13062_2021_299_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/af785aa76464/13062_2021_299_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/4f32f41f524a/13062_2021_299_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/f8530d652306/13062_2021_299_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b7/8734353/4927984024bc/13062_2021_299_Fig4_HTML.jpg

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