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

Lu, Nan1,2,3; Jiang, Qiming1,3,4,5; Xu, Tianshu1,3,4,6; Gao, Qiyuan1,2,3; Wang, Yuepeng1,3,4; Huang, Zixian1,3,4; Huang, Zhiquan1,3,4; Xu, Xiaoding1,2,3

2024-09-30

10.1186/s13046-024-03190-w

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH   影响因子和分区

1756-9966

BackgroundLong 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.MethodsWe 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.ResultsWe 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.ConclusionsOur results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

OSCC metastasis lncOCMRL1 EMT Nanoparticles siRNA delivery

SCI

英语

其他

National Natural Science Foundation of China["82173392","82303563","81802700"] ; Science and Technology Program of Guangdong["2024B1515040006","2023A1515010567","2021A1515111121"] ; Guangzhou Science and Technology Project["2024A03J0846","2023B03J1242","SL2022A04J01681"] ; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University[KLB09001] ; Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology[[2013]163]

Oncology

Oncology

WOS:001324333800005

BMC

CLINICAL MEDICINE

Web of Science

1.Sun Yat Sen Univ, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangdong Hong Kong Joint Lab RNA Med, Med Res Ctr,Sun Yat Sen Mem Hosp, Guangzhou 510120, Guangdong, Peoples R China
2.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou Key Lab Med Nanomat, Guangzhou 510120, Peoples R China
3.Sun Yat Sen Mem Hosp, Nanhai Translat Innovat Ctr Precis Immunol, Foshan 528200, Peoples R China
4.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Oral & Maxillofacial Surg, Guangzhou 510120, Guangdong, Peoples R China
5.Shenzhen Univ, Affiliated Shenzhen Stomatol Hosp, Dept Prosthodont & Implantol, Shenzhen 518001, Peoples R China
6.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Joint Lab Guangdong Hong Kong Univ Vasc Homeostasi, Shenzhen 518001, Peoples R China

Lu, Nan,Jiang, Qiming,Xu, Tianshu,et al. LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2024,43(1).

Lu, Nan.,Jiang, Qiming.,Xu, Tianshu.,Gao, Qiyuan.,Wang, Yuepeng.,...&Xu, Xiaoding.(2024).LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,43(1).

Lu, Nan,et al."LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 43.1(2024).