MALAT1, a long non-coding RNA, is highly expressed in cervical cancer cells and plays an important role in the development of cervical cancer. However, the mechanism for the excessive expression of MALAT1 in cervical cancer remains unclear. High-risk HPVs are causative agents of cervical cancer and the IL-6/STAT3 signaling is closely correlated with the development of various cancers including cervical cancer. In this study, the roles of HPV18 E6/E7 and IL-6/STAT3 in the regulation of MALAT1 transcription in cervical cancer cells were investigated. It was found that HPV18 E6/E7 activated the IL-6/STAT3 signaling and, in reciprocal, IL-6/STAT3 strengthened HPV18 E6/E7 expression in HeLa cells. Both HPV18 E6/E7 and IL-6/STAT3 were involved in MALAT1 expression and they worked synergistically in the upregulation of MALAT1 gene. With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. Taken together, our data suggest that IL-6/STAT3 mediates the HPV18 E6/E7 stimulated upregulation of MALAT1 gene in cervical cancer HeLa cells.

中文翻译：

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IL-6 / STAT3介导HPV18 E6 / E7刺激宫颈癌HeLa细胞中MALAT1基因的上调。

MALAT1是一种长的非编码RNA，在子宫颈癌细胞中高度表达，并在子宫颈癌的发生中起重要作用。但是，MALAT1在宫颈癌中过度表达的机制仍不清楚。高危HPV是宫颈癌的病原体，IL-6 / STAT3信号传导与包括宫颈癌在内的多种癌症的发生密切相关。在这项研究中，研究了HPV18 E6 / E7和IL-6 / STAT3在宫颈癌细胞MALAT1转录调控中的作用。发现HPV18 E6 / E7激活了IL-6 / STAT3信号传导，并且相反，IL-6 / STAT3增强了HeLa细胞中HPV18 E6 / E7的表达。HPV18 E6 / E7和IL-6 / STAT3均参与MALAT1的表达，并且在MALAT1基因的上调中起协同作用。使用萤光素酶报告基因分析，已证明MALAT1基因增强子区域中的STAT3结合序列对于IL-6或STAT3诱导的MALAT1启动子激活至关重要。两者合计，我们的数据表明IL-6 / STAT3介导HPV18 E6 / E7刺激宫颈癌HeLa细胞中MALAT1基因的上调。