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Int J Biol Sci 2017; 13(11):1398-1408. doi:10.7150/ijbs.22249

Research Paper

Targeting the long noncoding RNA MALAT1 blocks the pro-angiogenic effects of osteosarcoma and suppresses tumour growth

Zhi-Chang Zhang1*, Chun Tang2*, Yang Dong1, Jing Zhang1, Ting Yuan1, Shi-Cong Tao1✉, Xiao-Lin Li1✉

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.

Abstract

Osteosarcoma (OS), the commonest primary malignant tumour originating from bone, affects a substantial number of people, mostly during adolescent growth, and leads to a very poor prognosis as a result of the high rate of early metastases. Consequently, there is urgent demand for a novel treatment for this disease. There are growing concerns focused on OS-induced pro-angiogenic effects, but to date, the mechanism of OS-induced pro-angiogenesis is still insufficiently well-understood. Long noncoding RNAs (lncRNAs) have attracted increasing interest due to their strong correlation with a variety of diseases and their powerful capacity for epigenetic regulation. Recently, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a lncRNA, has been discovered to be closely related to OS progression and hypoxia responses which are associated with angiogenesis. In this study, we confirm that MALAT1 induces pro-angiogenic effects, and demonstrate that the underlying mechanism involves a MALAT1/mechanistic target of rapamycin (mTOR)/hypoxia inducible factor-1α (HIF-1α) loop. With the help of chemically-modified small interfering RNAs targeting MALAT1 (siMALAT1), we confirm that siMALAT could provide a potential strategy to block the abnormally active OS-induced pro-angiogenic effect, and ultimately successfully suppress progression of OS tumours.

Keywords: osteosarcoma, MALAT1, siRNA, angiogenesis, oncotherapy.

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How to cite this article:
Zhang ZC, Tang C, Dong Y, Zhang J, Yuan T, Tao SC, Li XL. Targeting the long noncoding RNA MALAT1 blocks the pro-angiogenic effects of osteosarcoma and suppresses tumour growth. Int J Biol Sci 2017; 13(11):1398-1408. doi:10.7150/ijbs.22249. Available from http://www.ijbs.com/v13p1398.htm