Background

Cervical cancer is the common gynecological deadly malignancy worldwide. Here we attempted to evaluate the effects and mechanisms of microRNA-501-5p (miR-501) on the cell proliferation, migration, invasion and the clinical significance in the cervical cancer.

Methods

Cervical cancer HeLa cells were transfected with miR-501 mimic or inhibitor or siRNA against Cylindromatosis (CYLD) using Lipofectamine 2000. miR-501 expression was assessed in HeLa cells and cervical cancer specimens by real-time qRT-PCR. The functional roles of miR-501 were determined by CCK-8, colony formation, scratch wound healing and transwell assays. The apoptosis rate was detected by flow cytometry assay. CYLD, BCL-2, BAX, NF-$\kappa$B p65 and phosphorylated p65 (p-p65) proteins were examined by Western blotting. CYLD expression was evaluated by immunohistochemistry in cervical cancer tissues.

Results

miR-501 was upregulated, whereas CYLD protein was downregulated in cervical cancer tissues compared to normal cervical tissues. miR-501 overexpression and CYLD protein downregulation were positively correlated with poor differentiation, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. CYLD was downregulated by miR-501 at both mRNA and protein levels in HeLa cells. miR-501 promoted cell proliferation, migration and invasion in cervical cancer, while inhibited the apoptosis. This is possibly due to the downregulation of CYLD and subsequent activation of NF-κB p65.

Conclusions

miR-501 upregulation and CYLD downregulation are associated with the development and progression of cervical cancer. miR-501 promotes cervical cancer cell proliferation, migration and invasion possibly via downregulating CYLD and subsequently activating NF-κB p65. miR-501 might be a potential therapeutic target for cervical cancer.

中文翻译：

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miR-501在宫颈癌中上调，并通过靶向CYLD促进细胞增殖，迁移和侵袭

背景

宫颈癌是全世界常见的妇科致命恶性肿瘤。在这里，我们试图评估microRNA-501-5p（miR-501）对子宫颈癌细胞增殖，迁移，侵袭的影响及其临床意义。

方法

使用Lipofectamine 2000，用miR-501模拟物或针对圆柱体病（CYLD）的抑制剂或siRNA转染宫颈癌HeLa细胞。通过实时qRT-PCR评估HeLa细胞和宫颈癌标本中的miR-501表达。miR-501的功能作用通过CCK-8，菌落形成，刮擦伤口愈合和transwell分析来确定。用流式细胞仪检测细胞凋亡率。CYLD，BCL-2，BAX，NF-$\kappa$通过蛋白质印迹检查了B p65和磷酸化的p65（p-p65）蛋白。CYLD表达通过免疫组织化学在宫颈癌组织中评估。

结果

与正常宫颈组织相比，宫颈癌组织中的miR-501上调，而CYLD蛋白则下调。miR-501过表达和CYLD蛋白下调与不良分化，肿瘤大小，国际妇产科联合会（FIGO）分期和淋巴结转移呈正相关。在HeLa细胞的mRNA和蛋白质水平上，miR-501均会下调CYLD。miR-501促进宫颈癌中的细胞增殖，迁移和侵袭，同时抑制细胞凋亡。这可能是由于CYLD的下调和随后NF-κBp65的激活所致。

结论

miR-501的上调和CYLD的下调与宫颈癌的发生和发展有关。miR-501可能通过下调CYLD并随后激活NF-κBp65来促进宫颈癌细胞的增殖，迁移和侵袭。miR-501可能是宫颈癌的潜在治疗靶标。