LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway.

IF 11.4 1区医学 Q1 ONCOLOGY Journal of Experimental & Clinical Cancer Research Pub Date : 2024-09-30 DOI:10.1186/s13046-024-03190-w

Nan Lu, Qiming Jiang, Tianshu Xu, Qiyuan Gao, Yuepeng Wang, Zixian Huang, Zhiquan Huang, Xiaoding Xu

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Abstract

Background: Long noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy.

Methods: We analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy.

Results: We determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis.

Conclusions: Our results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

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LncOCMRL1 通过 RRM2/EMT 通路促进口腔鳞状细胞癌的生长和转移。

背景：长非编码RNA（lncRNA）广泛参与癌症的发生和发展，但大多数lncRNA的功能尚未阐明。转移是制约包括口腔鳞状细胞癌（OSCC）在内的各种癌症治疗效果的主要因素。因此，探索调控OSCC转移的关键lncRNA并阐明其分子机制将有助于开发有效治疗OSCC的新策略：我们分析了有和无颈淋巴结转移的OSCC患者肿瘤组织以及OSCC细胞系的lncRNA表达谱。我们发现，在有淋巴结转移的OSCC患者肿瘤组织和高度转移的OSCC细胞系中，口腔鳞状细胞癌转移相关lncRNA 1（lncOCMRL1）的表达量很高。通过qRT-PCR、Transwell、集落形成和细胞增殖实验探讨了敲除lncOCMRL1对OSCC细胞侵袭、迁移和增殖能力的影响。通过 RNA pull-down、银染色、质谱分析、RIP 和 WB 实验探讨了 lncOCMRL1 促进 OSCC 转移和增殖的机制。为了提高其转化潜力，我们开发了一种还原反应纳米递送系统来递送 siRNA 用于抗肿瘤治疗：我们发现lncOCMRL1在OSCC转移性肿瘤组织和细胞中高表达。功能研究表明，lncOCMRL1的高表达可促进OSCC细胞在体内和体外的生长和转移。从机理上讲，lncOCMRL1可通过抑制RRM2泛素化诱导上皮-间质转化（EMT），从而促进OSCC细胞的增殖、侵袭和迁移。我们进一步构建了还原反应纳米颗粒（NPs），用于全身性递送靶向lncOCMRL1的siRNAs，并证明它们能高效抑制lncOCMRL1在体内的表达，显著抑制OSCC肿瘤的生长和转移：我们的研究结果表明，lncOCMRL1是阻断OSCC淋巴结转移的可靠靶点。

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

Journal of Experimental & Clinical Cancer Research 医学-肿瘤学

CiteScore

18.20

自引率

1.80%

发文量

333

审稿时长

1 months

期刊介绍： The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.