High-risk human papillomavirus (HR-HPV) infection is a major risk factor for the initiation and progression of cervical cancer (CC). This study aimed to explore the role of histone deacetylase 6 (HDAC6) in HPV-positive CC and the molecules implicated. Differentially expressed genes between HPV-positive and HPV-negative tissues, and differentially expressed microRNAs (miRNAs) in cells after HDAC6 downregulation were identified using microarray analyses. The expression profiles of HDAC6 and miR-199a and their cellular functions were investigated via loss-of-function studies. Xenograft tumors were induced in mice for in vivo studies. HDAC6 and Wnt5a were highly expressed, whereas miR-199a was poorly expressed in HPV-positive CC tissues. Downregulation of HDAC6 reduced proliferation, migration, invasion, and resistance to apoptosis of HPV-positive CC cells. HDAC6 suppressed the transcription of miR-199a, and miR-199a targeted Wnt5a to inactivate the Wnt signaling pathway. Further downregulation of miR-199a blocked the inhibitory effect of HDAC6 silencing on CC cell growth both in vivo and in vitro, whereas further artificial inhibition of Wnt5a inactivated Wnt signaling and blocked the malignant behaviors of CC cells. This study showed that HDAC6 suppresses the transcription of miR-199a and enhances the progression of HPV-positive cervical cancer through upregulation of Wnt5a.

高危人乳头瘤病毒 (HR-HPV) 感染是宫颈癌 (CC) 发生和发展的主要危险因素。本研究旨在探讨组蛋白去乙酰化酶 6 (HDAC6) 在 HPV 阳性 CC 中的作用和相关分子。使用微阵列分析鉴定了 HPV 阳性和 HPV 阴性组织之间差异表达的基因，以及 HDAC6 下调后细胞中差异表达的微 RNA (miRNA)。通过功能丧失研究研究了 HDAC6 和 miR-199a 的表达谱及其细胞功能。在小鼠体内诱导异种移植肿瘤学习。HDAC6 和 Wnt5a 高表达，而 miR-199a 在 HPV 阳性 CC 组织中低表达。HDAC6 的下调减少了 HPV 阳性 CC 细胞的增殖、迁移、侵袭和对细胞凋亡的抵抗。HDAC6 抑制 miR-199a 的转录，miR-199a 靶向 Wnt5a 以灭活 Wnt 信号通路。miR-199a 的进一步下调在体内和体外阻断了 HDAC6 沉默对 CC 细胞生长的抑制作用，而 Wnt5a 的进一步人工抑制使 Wnt 信号传导失活并阻断了 CC 细胞的恶性行为。该研究表明，HDAC6 通过上调 Wnt5a 抑制 miR-199a 的转录并促进 HPV 阳性宫颈癌的进展。