Ma Huiling, Liu Chao, Zhang Shuiting, Yuan Wenhui, Hu Junli, Huang Donghai, Zhang Xin, Liu Yong, Qiu Yuanzheng
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.
Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, China.
J Cancer. 2021 Sep 9;12(21):6519-6530. doi: 10.7150/jca.60743. eCollection 2021.
Migration and invasion are the initial step in the metastatic process, while metastasis is responsible for the poor prognosis of head and neck squamous cell carcinoma (HNSCC). Since miRNA has been found as an important regulator of gene expression at the post-transcriptional level in various diseases including carcinoma, exploring the role of miRNA in cancer metastasis will facilitate the target therapy of advanced HNSCC. MiR-328-3p has been reported to be an onco-miRNA or a tumor suppressor in several cancers. However, the role of miR-328-3p in HNSCC migration and invasion remains undefined. In this study, we first demonstrated that miR-328-3p enhanced migration and invasion of HNSCC , accompanying with a promotion of epithelial-mesenchymal transition (EMT) and mTOR activity. Meanwhile, we confirmed that miR-328-3p directly targeted the 3'UTR of H2A histone family, member X (H2AFX), which served as a tumor suppressor in migration and invasion of HNSCC. Moreover, H2AFX could partially reverse the migration and invasion of HNSCC caused by miR-328-3p. Overall, our results indicated that miR-328-3p enhanced migration and invasion of HNSCC through targeting H2AFX and activated the mTOR pathway.
迁移和侵袭是转移过程的起始步骤，而转移是头颈部鳞状细胞癌（HNSCC）预后不良的原因。由于miRNA已被发现是包括癌症在内的各种疾病转录后水平基因表达的重要调节因子，探索miRNA在癌症转移中的作用将有助于晚期HNSCC的靶向治疗。据报道，miR-328-3p在几种癌症中是一种癌miRNA或肿瘤抑制因子。然而，miR-328-3p在HNSCC迁移和侵袭中的作用仍不明确。在本研究中，我们首先证明miR-328-3p增强了HNSCC的迁移和侵袭，同时促进了上皮-间质转化（EMT）和mTOR活性。同时，我们证实miR-328-3p直接靶向H2A组蛋白家族成员X（H2AFX）的3'UTR，H2AFX在HNSCC的迁移和侵袭中起肿瘤抑制作用。此外，H2AFX可以部分逆转miR-328-3p引起的HNSCC的迁移和侵袭。总体而言，我们的结果表明，miR-328-3p通过靶向H2AFX增强了HNSCC的迁移和侵袭，并激活了mTOR通路。
