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miR-155-5p 通过 mTOR 通路抑制 PDK1 并促进宫颈癌中的自噬。

MiR-155-5p inhibits PDK1 and promotes autophagy via the mTOR pathway in cervical cancer.

机构信息

The Second Hospital of Tianjin Medical University, 300211 Tianjin, China.

Department of Gynecology and Obstetrics, Affiliated Tongji Hospital, Tongji University, Shanghai, China.

出版信息

Int J Biochem Cell Biol. 2018 Jun;99:91-99. doi: 10.1016/j.biocel.2018.04.005. Epub 2018 Apr 5.

Abstract

Cervical cancer is one of the most common malignant tumors and the leading cause of cancer-related mortality in women. Persistent cervical infection by high-risk human papillomavirus (hrHPV) is related to cervical cancer. MicroRNAs could regulate autophagy caused by viral infection. The aim of the present study was to investigate the regulation of autophagy by miR-155-5p in cervical cancer. In HPV+ human cervical lesion tissues, miR-155-5p expression was found to be markedly decreased. Compared to C33A cancer cells (HPV-), the miR-155-5p expression was significantly lower in Siha and HeLa cells (HPV+), which are both hrHPV positive. The level of autophagy was higher in C33A cells than in Siha and HeLa cells. In addition, in C33A, Siha and HeLa cervical cancer cells, miR-155-5p overexpression promoted autophagy, whereas miR-155-5p downregulation had the opposite effects. Furthermore, miR-155-5p downregulation suppressed LC3 and promoted P62 protein expression in C33A cells through promoting the PDK1/mTOR pathway, whereas miR-155-5p overexpression recovered LC3 and suppressed P62 protein expression by suppressing PDK1/mTOR signaling. Taken together, our results indicate the importance of miR-155-5p in cervical cancer cells and suggest a novel mechanism of hrHPV in promoting cervical lesions.

摘要

宫颈癌是最常见的恶性肿瘤之一,也是导致女性癌症相关死亡的主要原因。高危型人乳头瘤病毒(hrHPV)持续感染与宫颈癌有关。微小 RNA 可以调节病毒感染引起的自噬。本研究旨在探讨 miR-155-5p 在宫颈癌中对自噬的调节作用。在 HPV+的人宫颈病变组织中,发现 miR-155-5p 的表达明显降低。与 C33A 癌细胞(HPV-)相比,Siha 和 HeLa 细胞(HPV+)中 miR-155-5p 的表达显著降低,且均为高风险 HPV 阳性。C33A 细胞中的自噬水平高于 Siha 和 HeLa 细胞。此外,在 C33A、Siha 和 HeLa 宫颈癌细胞中,miR-155-5p 的过表达促进了自噬,而 miR-155-5p 的下调则产生相反的效果。此外,miR-155-5p 的下调通过促进 PDK1/mTOR 通路促进 C33A 细胞中 LC3 和 P62 蛋白的表达,而 miR-155-5p 的过表达通过抑制 PDK1/mTOR 信号来恢复 LC3 并抑制 P62 蛋白的表达。综上所述,我们的研究结果表明 miR-155-5p 在宫颈癌细胞中的重要性,并提示了 hrHPV 促进宫颈病变的新机制。

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