Downregulation of the lncRNA RP11-432I5.4 inhibits tumorigenesis in the JAK2V617F-positive classic myeloproliferative neoplasms

Abstract Background: Although aberrant expression of long non-coding RNA (lncRNA) is associated with many human cancers, little is known about its role in the JAK2V617F-positive classic myeloproliferative neoplasms (cMPNs). Methods: In this study, we performed a comprehensive analysis of lncRNAs in human cMPNs cells using a lncRNA cDNA microarray and identified the lncRNA RP11-432I5.4 acted as an effective factor in JAK2V617F-positive cMPN cells. Results: The lncRNA RP11-432I5.4 showed higher expression in cMPN patients, especially higher in JAK2V617F-positive cells compared with JAK2V617F-negative cells. Overexpression of lncRNA RP11-432I5.4 increased the proliferation of JAK2V617F-positive cells while downregulation of it decreased proliferation, promoted apoptosis and triggered S phase arrest of JAK2V617F-positive cells. Furthermore, in a mouse xenograft model, the silencing of lncRNARP11-432I5.4 repressed tumor formation in vivo. Conclusions: Taken together, these results revealed that lncRNA RP11-432I5.4 plays an important role in cMPN tumorigenesis and may be a potential novel target for treatment of JAK2V617F-positive cMPN patients.