Theranostics 2017; 7(15):3768-3780. doi:10.7150/thno.20796
The Bidirectional Regulation between MYL5 and HIF-1α Promotes Cervical Carcinoma Metastasis
1. Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China;
2. The First Affiliated Hospital of Sun Yat-sen University Guangzhou 510080, People's Republic of China;
3. The Second Affiliated Hospital, Nanchang University, Nanchang 330000, P. R. China.
* These authors contributed equally to this work
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 in vitro and in vivo 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.
Keywords: MYL5, cervical cancer, oxygen regulation.
Zhang L, Huang ST, Feng YL, Wan T, Gu HF, Xu J, Yuan LJ, Zhou Y, Yu XJ, Huang L, Luo RZ, Jia WH, Zheng M. The Bidirectional Regulation between MYL5 and HIF-1α Promotes Cervical Carcinoma Metastasis. Theranostics 2017; 7(15):3768-3780. doi:10.7150/thno.20796. Available from http://www.thno.org/v07p3768.htm