Zheng Zhiming, Zhang Yongchao, Zhang Zhen, Yang Yihang, Song Tao
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland).
Med Sci Monit. 2017 Mar 13;23:1277-1285. doi: 10.12659/msm.900092.
BACKGROUND Pituitary adenomas are mostly benign tumors, although certain cases have invasiveness, which might be related with high expression of miR-106b. The PTEN-PI3K/AKT signal pathway is known to be related with cell migration and invasion. Among these, PTEN is the target gene for miR-106b. Whether miR-106b affects invasiveness of pituitary adenoma via PTEN-PI3K/AKT is unclear. MATERIAL AND METHODS Both invasive and non-invasive pituitary adenoma tissue samples were collected from our Neurosurgery Department, in parallel with brain tissues after head contusion surgery. Pituitary adenoma cell line HP75 was cultured in vitro and divided into NC and miR-106b inhibitor groups for measuring cell cycle/proliferation. Malignant growth of cells was measured by agarose gel clonal assay, while cell migration and invasion were reflected by starch assay and Transwell assay, respectively. The expression of PTEN, PI3K/AKT, and MMP-9 was measured. RESULTS MiR-106b was significantly up-regulated in pituitary adenoma but PTEN was down-regulated, especially in invasive tumors. The inhibition of miR-106b remarkably suppressed proliferation and anchorage-independent growth of HP75 cells, with major arrest of cell cycles. The inhibition of miR-106b significantly depressed starch healing and invasive potency of cells. A negative targeted regulation existed between miR-106b and PTEN, as the inhibition of miR-106b significantly enhanced PTEN expression, affecting the activity of downstream PI3K/AKT signaling pathway, thus affecting migration and invasion of pituitary adenoma. CONCLUSIONS MiR-106b can affect migration and invasion of pituitary adenoma cells via regulating PTEN and further activity of the PI3K/AKT signaling pathway and MMP-9 expression.
垂体腺瘤大多为良性肿瘤，尽管某些病例具有侵袭性，这可能与miR - 106b的高表达有关。已知PTEN - PI3K/AKT信号通路与细胞迁移和侵袭有关。其中，PTEN是miR - 106b的靶基因。miR - 106b是否通过PTEN - PI3K/AKT影响垂体腺瘤的侵袭性尚不清楚。
从我院神经外科收集侵袭性和非侵袭性垂体腺瘤组织样本，并与头部挫伤手术后的脑组织并行收集。体外培养垂体腺瘤细胞系HP75，分为NC组和miR - 106b抑制剂组，用于检测细胞周期/增殖。通过琼脂糖凝胶克隆试验检测细胞的恶性生长，而细胞迁移和侵袭分别通过淀粉试验和Transwell试验反映。检测PTEN、PI3K/AKT和MMP - 9的表达。
miR - 106b在垂体腺瘤中显著上调，但PTEN下调，尤其是在侵袭性肿瘤中。抑制miR - 106b可显著抑制HP75细胞的增殖和非锚定依赖性生长，使细胞周期主要停滞。抑制miR - 106b可显著降低细胞的淀粉愈合能力和侵袭能力。miR - 106b与PTEN之间存在负向靶向调控，抑制miR - 106b可显著增强PTEN表达，影响下游PI3K/AKT信号通路的活性，从而影响垂体腺瘤的迁移和侵袭。
miR - 106b可通过调节PTEN以及PI3K/AKT信号通路的进一步活性和MMP - 9表达来影响垂体腺瘤细胞的迁移和侵袭。
