Wu Xiaorong, Cao XiaoBin, Chen Fanghong
Department of Gynecology and Obstetrics, Ankang Central Hospital of Shanxi Province, Shanxi, 710000, China.
Department of Gynecology and Obstetrics, Tongcuan Maternal and Child Health Hospital of Shanxi Province, Shanxi, 710000, China.
Oncol Res. 2017 Aug 31. doi: 10.3727/096504017X15037515496840.
Cervical cancer is the second most common malignant cancer in females. Recent findings indicate that LncRNA-HOTAIR played a crucial role in tumor progression. In our present study, we aimed to explore the regulating role of HOTAIR in the progression of cervical cancer. The expression of HOTAIR was found up-regulated in cervical cancer tissues and cell lines (Hela, CasKi, Me180 and C-33A) compared with the normal tissues and normal cervical cell line (Ect1/E6E7). To examine the function of HOTAIR, gene knockdown (KD) was performed using HOTAIR short hairpin RNAs (shRNAs). HOTAIR shRNA significantly suppressed cells proliferation and migration in Hela cells. Besides that, the targeting relationship between HOTAIR and miR-326 was firstly revealed by bioinformatics prediction. Simultaneously, suppressed expression of miR-326 was detected in tumor tissues and cell lines compared with the control. Then, suppressed expression level of miR-326 was elevated by adding miR-326 mimic in cervical cancer cells transfected with LncR-HOTAIR. Similarly, increased expression level of miR-326 was reduced by adding miR-326 inhibitor in cervical cancer cells transfected with HOTAIR shRNA. The targeting relationship between HOTAIR and miR-326 was further been confirmed through the luciferase report assay. Moreover, there existed a negative relationship between the expression of HOTAIR and miR-326. In addition, enhanced cell proliferation and migration abilities were suppressed by HOTAIR shRNA in cells transfected with miR-326 inhibitor. Finally, the in vivo experiment revealed that tumor growth and metastasis could also be inhibited by HOTAIR shRNA. Our present study elucidated the regulating role of HOTAIR/miR-326 axis in cervical cancer progression and provided a new potential therapeutic strategy for cervical cancer.
宫颈癌是女性中第二常见的恶性肿瘤。最近的研究结果表明，长链非编码RNA-HOTAIR在肿瘤进展中起关键作用。在我们目前的研究中，我们旨在探讨HOTAIR在宫颈癌进展中的调控作用。与正常组织和正常宫颈细胞系（Ect1/E6E7）相比，发现HOTAIR在宫颈癌组织和细胞系（Hela、CasKi、Me180和C-33A）中表达上调。为了检测HOTAIR的功能，使用HOTAIR短发夹RNA（shRNA）进行基因敲低（KD）。HOTAIR shRNA显著抑制了Hela细胞的增殖和迁移。除此之外，通过生物信息学预测首次揭示了HOTAIR与miR-326之间的靶向关系。同时，与对照组相比，在肿瘤组织和细胞系中检测到miR-326表达受到抑制。然后，在转染了LncR-HOTAIR的宫颈癌细胞中添加miR-326模拟物，可提高miR-326的表达水平。同样，在转染了HOTAIR shRNA的宫颈癌细胞中添加miR-326抑制剂，可降低miR-326的表达水平。通过荧光素酶报告基因检测进一步证实了HOTAIR与miR-326之间的靶向关系。此外，HOTAIR与miR-326的表达之间存在负相关关系。此外，在转染了miR-326抑制剂的细胞中，HOTAIR shRNA抑制了细胞增殖和迁移能力的增强。最后，体内实验表明，HOTAIR shRNA也可抑制肿瘤生长和转移。我们目前的研究阐明了HOTAIR/miR-326轴在宫颈癌进展中的调控作用，并为宫颈癌提供了一种新的潜在治疗策略。
