HOTTIP/HOXA13 axis is positively associated with cell proliferation in glioma

Glioma ranks as the most frequent type of primary brain tumor occurring in the central nervous system of adults. Recent evidence highlights the long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) as a crucial determinant in the progression of human cancers. The present study was to examine the functions and mechanisms of HOTTIP in regulating glioma tumorigenesis. The expression of HOTTIP in 20 glioma tissues and 10 non-cancerous brain tissues was determined by qRT-PCR. Both RNA interference (RNAi) and overexpression approaches were utilized to study the functions of HOTTIP in LN229 cell proliferation, by using CCK-8 and flow cytometry assays. We uncovered that HOTTIP was upregulated in gliomas when compared with non-cancerous brain tissues. Knockdown of HOTTIP significantly inhibited cell proliferation and induced G0/G1 arrest in vitro, while overexpression of HOTTIP led to the opposite effects. Furthermore, we observed the marked upregulation of HOXA13 by HOTTIP in LN229 cells, and knockdown of HOXA13 by RNAi revealed that HOTTIP promoted glioma cell proliferation at least partly by regulating HOXA13. Finally, by correlating the expression data and analyzing the prognosis value of HOTTIP and HOXA13 in gliomas, we verified that the levels of HOTTIP and HOXA13 are positively associated with each other. The expression of HOTTIP and HOXA13 were both associated with higher tumor grade. Our study identifies the key role of HOTTIP/HOXA13 axis in cell proliferation of glioma and provides novel insights on the functions of lncRNA in glioma.