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通过RNA干扰沉默SOX2表达可抑制人喉癌TU212细胞的增殖、侵袭和转移,并通过MAP4K4/JNK信号通路诱导细胞凋亡。

Silencing SOX2 Expression by RNA Interference Inhibits Proliferation, Invasion and Metastasis, and Induces Apoptosis through MAP4K4/JNK Signaling Pathway in Human Laryngeal Cancer TU212 Cells.

作者信息

Yang Ning, Wang Yan, Hui Lian, Li Xiaotian, Jiang Xuejun

机构信息

Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China (NY, YW, LH, XL, XJ)

出版信息

J Histochem Cytochem. 2015 Sep;63(9):721-33. doi: 10.1369/0022155415590829. Epub 2015 May 22.

Abstract

SRY (sex determining region Y)-box 2 (SOX2) plays an important role in tumor cell metastasis and apoptosis. Laryngeal squamous cell carcinoma (LSCC), responsible for 1.5% of all cancers, is one of the most common head and neck malignancies. Accumulating evidence shows that SOX2 is overexpressed in several human tumors, including lung cancer, esophageal carcinoma, pancreatic carcinoma, breast cancer, ovarian carcinoma and glioma. Our study aimed to investigate the silencing effects of SOX2 expression using RNA interference (RNAi) on various biological processes in laryngeal cancer TU212 cells, including proliferation, apoptosis, invasion and metastasis. We also studied the involvement of the MAPK/JNK signaling pathway in the biological effects of SOX2 siRNA in TU212 cells. We found that silencing SOX2 decreased the proliferation, migration, and invasion of TU212 cells, and induced apoptosis. This effect of silencing SOX2 could be reversed by silencing MAP4K4. Therefore, we consider SOX2 as a key regulator of the upstream MAP4K4/JNK signaling pathways that could be a potential therapeutic target in the treatment of patients with or prevention of laryngeal cancer.

摘要

SRY(Y染色体性别决定区)-盒2(SOX2)在肿瘤细胞转移和凋亡中发挥重要作用。喉鳞状细胞癌(LSCC)占所有癌症的1.5%,是最常见的头颈恶性肿瘤之一。越来越多的证据表明,SOX2在包括肺癌、食管癌、胰腺癌、乳腺癌、卵巢癌和神经胶质瘤在内的多种人类肿瘤中过度表达。我们的研究旨在探讨使用RNA干扰(RNAi)沉默SOX2表达对喉癌TU212细胞各种生物学过程的影响,包括增殖、凋亡、侵袭和转移。我们还研究了MAPK/JNK信号通路在TU212细胞中SOX2 siRNA生物学效应中的作用。我们发现沉默SOX2可降低TU212细胞的增殖、迁移和侵袭,并诱导凋亡。沉默MAP4K4可逆转沉默SOX2的这种作用。因此,我们认为SOX2是上游MAP4K4/JNK信号通路的关键调节因子,可能是喉癌患者治疗或预防的潜在治疗靶点。

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