====== HOTAIR ======

HOTAIR (for HOX transcript antisense RNA) is a human gene located on [[chromosome 12]]. It is the first example of an RNA expressed on one chromosome that has been found to influence transcription on another chromosome.


It has been considered as a negative prognostic factor in liver, colon, and laryngeal squamous cancer patients, and identified as a critical [[glioma biomarker]] for tumor grade, molecular subtype,
diagnosis, and prognosis.
((Zhang, J.X., Han, L., Bao, Z.S., Wang, Y.Y., Chen, L.Y., Yan, W., Yu, S.Z., Pu, P.Y., Liu,
N., You, Y.P., et al.; Chinese Glioma Cooperative Group (2013). HOTAIR, a cell
cycle-associated Long non-coding RNA and a strong predictor of survival, is preferentially
expressed in classical and mesenchymal glioma. Neuro-oncol. 15, 1595–1603.))
((Shen, J., Hodges, T.R., Song, R., Gong, Y., Calin, G.A., Heimberger, A.B., and Zhao, H.
(2018). Serum HOTAIR and GAS5 levels as predictors of survival in patients with
glioblastoma. Mol. Carcinog. 57, 137–141.))
((Tan, S.K., Pastori, C., Penas, C., Komotar, R.J., Ivan, M.E., Wahlestedt, C., and Ayad,
N.G. (2018). Serum Long non-coding RNA HOTAIR as a novel diagnostic and prognostic
biomarker in glioblastoma multiforme. Mol. Cancer 17, 74.)).

HOTAIR was reported to promote [[glioblastoma]] (GBM) [[cell cycle]] by regulating a predominant [[PRC2]] complex component [[EZH2]]
((Zhang, K., Sun, X., Zhou, X., Han, L., Chen, L., Shi, Z., Zhang, A., Ye, M., Wang, Q.,
Liu, C., et al. (2015). Long non-coding RNA HOTAIR promotes glioblastoma cell cycle
progression in an EZH2 dependent manner. Oncotarget 6, 537–546.)).

Knockdown of HOTAIR was found to exert a glioma-suppressive function by regulating the [[miR 326]]/[[FGF1]]-
signaling pathway in vitro and in vivo, indicating the HOTAIRmiR-326-FGF1 axis as a potential therapeutic strategy for glioma treatment
((Ke, J., Yao, Y.L., Zheng, J., Wang, P., Liu, Y.H., Ma, J., Li, Z., Liu, X.B., Li, Z.Q., Wang,
Z.H., and Xue, Y.X. (2015). Knockdown of long non-coding RNA HOTAIR inhibits
malignant biological behaviors of human glioma cells via modulation of miR-326.
Oncotarget 6, 21934–21949.)).

Knockdown of HOTAIR can also increase permeability of the blood-tumor barrier (BTB) by reducing tight junction-related proteins in glioma microvascular endothelial cells via the miR148b-3p/USF1
pathway, facilitating the delivery of antineoplastic drugs
((Sa, L., Li, Y., Zhao, L., Liu, Y., Wang, P., Liu, L., Li, Z., Ma, J., Cai, H., and Xue, Y.
(2017). The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability
of BTB. Front. Mol. Neurosci. 10, 194.)).

In addition, HOTAIR is a direct target of [[bromodomain]] and extraterminal (BET) domain proteins in GBM
((Pastori, C., Kapranov, P., Penas, C., Peschansky, V., Volmar, C.H., Sarkaria, J.N.,
Bregy, A., Komotar, R., St Laurent, G., Ayad, N.G., and Wahlestedt, C. (2015). The
Bromodomain protein BRD4 controls HOTAIR, a Long non-coding RNA essential
for glioblastoma proliferation. Proc. Natl. Acad. Sci. USA 112, 8326–8331.))
BET proteins are functional requisites for GBM cell growth and malignancy;
((Xu, L., Chen, Y., Mayakonda, A., Koh, L., Chong, Y.K., Buckley, D.L., Sandanaraj, E.,
Lim, S.W., Lin, R.Y., Ke, X.Y., et al. (2018). Targetable BET proteins- and E2F1-
dependent transcriptional program maintains the malignancy of glioblastoma.
Proc. Natl. Acad. Sci. USA 115, E5086–E5095.))
thus, targeting HOTAIR may block BET protein-induced malignancy of GBM and overcome resistance of GBM to BET bromodomain inhibitors (BBIs), which show broad anticancer effects.