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长链非编码 RNA PVT1 通过调节 TGF-β在口腔鳞状细胞癌中与癌相关成纤维细胞增殖相关。

LncRNAPVT1 is Associated with Cancer-Associated Fibroblasts Proliferation Through Regulating TGF-βin Oral Squamous Cell Carcinoma.

机构信息

Biomedical Laboratory, Medical School of Liaocheng University, Liaocheng, Shandong Province, P.R. China.

Department of Stomatology, Anqiu Municipal Hospital, Weifang, Shandong Province, P.R. China.

出版信息

Immunol Invest. 2024 Nov;53(8):1250-1263. doi: 10.1080/08820139.2024.2395874. Epub 2024 Aug 27.

Abstract

INTRODUCTION

Human oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown.

METHODS

Knockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with α-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-β were detected using ELISA assay.

RESULTS

We found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-β.

DISCUSSION

Our results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-β. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC.

摘要

简介

人口腔鳞状细胞癌(OSCC)是最常见的口腔癌类型,其存活率较低。OSCC 细胞与癌相关成纤维细胞(CAFs)之间的细胞间通讯在 OSCC 进展中发挥重要作用。我们之前证明 CAFs 促进 OSCC 细胞迁移和侵袭。然而,OSCC 细胞如何影响 CAFs 的增殖尚不清楚。

方法

使用慢病毒感染技术确认 PVT1 的敲低。使用免疫组织化学技术用 α-SMA 染色鉴定组织中的 CAFs。CCK-8 测定法用于评估细胞增殖。通过 qRT-PCR 测量基因的 mRNA 水平。使用 ELISA 测定法检测分泌的 TGF-β。

结果

我们发现长链非编码 RNA(lncRNA)浆细胞瘤变异易位 1(PVT1)的敲低与小鼠异种移植瘤中 CAFs 的低密度有关;进一步分析表明,OSCC 细胞中的 PVT1 通过转化生长因子(TGF)-β诱导 CAF 增殖-β。

讨论

我们的研究结果表明,肿瘤细胞中的 lncRNA PVT1 通过调节 TGF-β 参与 OSCC 中 CAF 的发育。这项研究揭示了 PVT1 调节 OSCC 进展的新机制,并且 PVT1 是 OSCC 的潜在治疗靶点。

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