Title:Targeting HOTAIR induces mitochondria related apoptosis and inhibits tumor growth in head and neck squamous cell carcinoma in vitro and in vivo.
Volume: 15
Issue: 10
Author(s): L. Kong, X. Zhou, Y. Wu, Y. Wang, L. Chen, P. Li, S. Liu, S. Sun, Y. Ren, M. Mei, X. Wang and L. Zhang
Affiliation:
关键词:
HOTAIR
摘要: Homeobox (HOX) transcript antisense RNA (HOTAIR), a long
nuclear-retained noncoding RNA (lncRNA), is overexpressed in a variety of
human cancers. Increasing evidence shows that HOTAIR plays a vital role in cancer initiation and progression
by affecting cell cycle progress, apoptosis and invasion. However, whether HOTAIR serves as a target of
therapeutic potential and the underlying mechanism in head and neck squamous cell carcinoma (HNSCC) is
still unclear. Thus, we employed a HOTAIR specific siRNA to deplete its expression in two human HNSCC cell
lines, Tca8113 and Tscca. The flow cytometry (FCM) analysis showed that HOTAIR depletion induced tumor
cell apoptosis in vitro. JC-1 probe examination showed that the mitochondrial membrane potential was
changed significantly by HOTAIR blockage. Mitochondrial calcium uptake 1(MICU1) dependent cell death was
induced by HOTAIR depletion. Protein expression analysis indicated that mitochondrial related cell death
pathway (Bcl-2, BAX, Caspase-3, Cleaved Caspase-3, Cytochrome c) involved in HOTAIR dependent
apoptosis process. Moreover, a Tscca derived xenograft tumor model was employed to further validate that
injection of HOTAIR siRNA inhibited tumor growth. In summary, we suggested that HOTAIR inhibition could be
developed as a new therapeutic in HNSCC treatments.
