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, researchers at Shanghai Jiao Tong University 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), they 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.
Tumour volume was significantly smaller after siMALAT1 treatment.