J Cancer 2018; 9(1):71-80. doi:10.7150/jca.22113
Targeting LncRNA-MALAT1 suppresses the progression of osteosarcoma by altering the expression and localization of β-catenin
1. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China;
2. Department of Nursing, Guangming Traditional Chinese Medicine Hospital, Pudong New Area, Shanghai 201300, China.
* Co-first authors: These authors contributed equally to this work.
Zhang ZC, Tang C, Dong Y, Zhang J, Yuan T, Li XL. Targeting LncRNA-MALAT1 suppresses the progression of osteosarcoma by altering the expression and localization of β-catenin. J Cancer 2018; 9(1):71-80. doi:10.7150/jca.22113. Available from https://www.jcancer.org/v09p0071.htm
Osteosarcoma (OS), which affects adolescents especially during a growth spurt, has the highest incidence of any primary malignant bone tumour, and a high rate of early metastasis leading to a very poor prognosis. In recent years, non-coding RNAs, especially long non-coding RNAs (lncRNAs) have attracted more and more attention as novel epigenetic regulators in a variety of tumours, including OS. Most recently, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was found to play an important role in OS progression by modulating the enhancers of zeste homolog 2 (EZH2). Furthermore, MALAT1 could inhibit the expression of E-cadherin and promote the expression of β-catenin, and this phenomenon might be the outcome of MALAT1-induced EZH2 activation. In this study, we investigated the vital function of MALAT1 in the progression of OS and its potential leading mechanism, altering the expression and localization of β-catenin via epigenetic transcriptional regulation by interacting with EZH2. With the help of MALAT1 silencing using small interfering RNAs (siRNAs), the loss of E-cadherin of MNNG/HOS cells was rescued, and the abnormal expression and localization of β-catenin were corrected at the same time. Overall, our research showed promising potential for new treatment strategies based on epigenetic regulation targeting MALAT1, which will not only coordinate with the patient's immune system, but also eliminate OS in conjunction with chemotherapy.
Keywords: osteosarcoma, long non-coding RNA, MALAT1, E-cadherin, β-catenin.