Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
The First Affiliated Hospital of Sun Yat-sen University Guangzhou 510080, People's Republic of China.
Theranostics. 2017 Aug 23;7(15):3768-3780. doi: 10.7150/thno.20796. eCollection 2017.
Myosin light chains (MLC) serve important regulatory functions in a wide range of cellular and physiological processes. Recent research found that MLC are also chromatin-associated nuclear proteins which regulate gene transcription. In this study, the MLC member myosin regulatory light chain 5 (MYL5) expression was upregulated in late stage cervical cancer patients, positively correlated with pelvic lymph node metastasis, and identified as a poor survival indicator. MYL5 overexpression promoted metastasis in cervical cancer and models, whereas MYL5 silencing had the converse effect. We demonstrated a bidirectional regulation between MYL5 and hypoxia inducible factor-1α (HIF-1α). HIF-1α activates MYL5 via binding to the hypoxia response element (HRE) in the promoter of MYL5, and MYL5 could sustain HIF-1α expression by tethering to recognition sequence AGCTCC in the HIF-1α promoter region. Clinical data confirmed a positive correlation between MYL5 and HIF-1α. In summary, our data show that MYL5 may act as a prognosis predictive factor in cervical carcinoma, and strategies that inhibit the interaction of MYL5 and HIF-1α may benefit the cervical carcinoma patients with metastasis.
肌球蛋白轻链（MLC）在广泛的细胞和生理过程中发挥着重要的调节功能。最近的研究发现，MLC 也是与染色质相关的核蛋白，可调节基因转录。在这项研究中，晚期宫颈癌患者的肌球蛋白调节轻链 5（MYL5）表达上调，与盆腔淋巴结转移呈正相关，并被确定为预后不良的指标。MYL5 的过表达促进了宫颈癌的转移，而 MYL5 的沉默则产生了相反的效果。我们证明了 MYL5 和缺氧诱导因子-1α（HIF-1α）之间存在双向调节。HIF-1α 通过结合 MYL5 启动子中的缺氧反应元件（HRE）来激活 MYL5，而 MYL5 可以通过与 HIF-1α 启动子区域中的识别序列 AGCTCC 结合来维持 HIF-1α 的表达。临床数据证实了 MYL5 和 HIF-1α 之间存在正相关。总之，我们的数据表明，MYL5 可能是宫颈癌的预后预测因子，抑制 MYL5 和 HIF-1α 相互作用的策略可能使具有转移风险的宫颈癌患者受益。
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