High-risk (hr) human papillomaviruses (HPV) infection and integration has caused the majority of cervical cancer, of which E6 and E7 oncogenes are invariably retained and expressed to immortalize cells probably via affecting cell migration and invasion, and tumor metastasis. However, the underlying mechanism that mediates the procedure such as motility of cervical cancer cells within the tumor microenvironment is not well understood. Herein, we examined one possible factor—extracellular lactic acid, an end up chemical in glycolytic tumor cells, on the motility in HPV16 positive SiHa cells. The results showed that lactic acid enhanced cell migration and invasion behavior via stimulating the expression of miR-744. ARHGAP5 was confirmed to be a target of miR-744, and silencing ARHGAP5 exhibited an inhibiting effect on cell migration and invasion as that observed by suppressing miR-744. In addition, lactic acid down-regulated E6 and E7 protein levels, and overexpression of either miR-744 or ARHGAP5 could also reduce E6 and E7 levels. Overall, our findings suggest that the miR-774/ARHGAP5 axis may provide a vital role in triggering lactic acid-induced migration and invasion in SiHa cells, regardless of the diminished effect due to the partial inhibition of E6 and E7 expression.

高危（hr）人乳头瘤病毒（HPV）感染和整合已引起大多数子宫颈癌，其中E6和E7癌基因始终被保留并表达，可能通过影响细胞迁移和侵袭以及肿瘤转移而使细胞永生。然而，在肿瘤微环境中介导该过程例如宫颈癌细胞的运动性的潜在机制还不是很清楚。在本文中，我们检查了一个可能的因素-细胞外乳酸（糖酵解肿瘤细胞中的最终化学物质）对HPV16阳性SiHa细胞运动的影响。结果表明，乳酸通过刺激miR-744的表达增强了细胞的迁移和侵袭行为。ARHGAP5被确认为miR-744的靶标，通过抑制miR-744，ARHGAP5沉默可抑制细胞迁移和侵袭。此外，乳酸会下调E6和E7蛋白水平，而miR-744或ARHGAP5的过表达也会降低E6和E7水平。总体而言，我们的发现表明，miR-774 / ARHGAP5轴可能在触发乳酸诱导的SiHa细胞迁移和侵袭中起着至关重要的作用，而不管由于E6和E7表达的部分抑制而导致的作用减弱。