Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC. After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain- and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo. HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-β signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC. These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-β signaling pathway.

中文翻译：

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MicroRNA-495 通过 HOXC6 介导的 TGF-β 信号通路对口腔鳞状细胞癌中的癌症干细胞产生抑制作用。

口腔鳞状细胞癌 (OSCC) 与高发病率相关，在全球恶性肿瘤中排名第六。越来越多的证据表明，microRNAs（miRNAs 或 miRs）在调节癌症干细胞（CSCs）中发挥着关键作用，从而推动 OSCC 的增殖和扩散。因此，基于通过基因表达综合 (GEO) 分析对异常表达的 miR-495 和同源框 C6 (HOXC6) 的改变，我们随后探讨了 miR-495 对 OSCC 中 CSCs 进展的潜在影响。从 OSCC 患者的临床组织样本中分离出 CSCs 后，测定 miR-495 和 HOXC6 的表达，然后验证 miR-495 和 HOXC6 之间的关系。随后，进行增益和损失函数方法来检测 miR-495 和 HOXC6 在细胞增殖、迁移、OSCC 中 CSC 的侵袭、细胞周期进入、凋亡和上皮间质转化 (EMT) 以及体内肿瘤生长。HOXC6 在 OSCC 中高表达，而 miR-495 低表达。HOXC6被证实是miR-495的靶基因，miR-495可以抑制TGF-β信号通路的激活。具有 miR-495 过表达或 HOXC6 沉默的 CSC 表现出逆转的 EMT 过程；增殖、迁移和入侵能力降低；并在体外促进细胞凋亡。此外，在注射 miR-495 agomir 或 sh-HOXC6 后，在体内观察到抑制的肿瘤生长。相反，miR-495的下调在OSCC的进展中显示出诱导作用。这些发现表明 miR-495 可能抑制 HOXC6 以抑制 EMT、增殖、迁移、