miR-328-3p promotes migration and invasion by targeting H2AFX in head and neck squamous cell carcinoma.

miR-328-3p promotes migration and invasion by targeting H2AFX in head and neck squamous cell carcinoma.
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miR-328-3p通过靶向H2AFX促进头颈鳞状细胞癌的迁移和侵袭

DOI:
10.7150/jca.60743
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发表时间:
2021
期刊:
影响因子:
3.9
通讯作者:
Qiu Y
Qiu Y
中科院分区:
医学3区
文献类型:
--
作者:
Ma H;Liu C;Zhang S;Yuan W;Hu J;Huang D;Zhang X;Liu Y;Qiu Y

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迁移和侵袭是头颈部鳞状细胞癌转移过程的起始步骤,而转移是头颈部鳞状细胞癌预后不良的原因。由于miRNA在转录后水平调控基因表达,在包括肿瘤在内的多种疾病中发挥重要作用,因此研究miRNA在肿瘤转移中的作用将有助于晚期HNSCC的靶向治疗。据报道,miR-328- 3 p是几种癌症中的致癌miRNA或肿瘤抑制因子。然而,miR-328- 3 p在HNSCC迁移和侵袭中的作用仍不明确。在本研究中,我们首次证明了miR-328- 3 p在体外增强了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- 3 p直接靶向H2 A组蛋白家族成员X(H2 AFX)的3 'UTR,其在HNSCC的迁移和侵袭中起肿瘤抑制作用。H2 AFX可部分逆转miR-328- 3 p诱导的HNSCC迁移和侵袭。总之,我们的结果表明,miR-328- 3 p通过靶向H2 AFX增强HNSCC的迁移和侵袭,并激活mTOR通路。
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 in vitro, 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.
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