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. ¹⁾ ²⁾ ³⁾.

HOTAIR was reported to promote glioblastoma (GBM) cell cycle by regulating a predominant PRC2 complex component EZH2 ⁴⁾.

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 ⁵⁾.

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 ⁶⁾.

In addition, HOTAIR is a direct target of bromodomain and extraterminal (BET) domain proteins in GBM ⁷⁾ BET proteins are functional requisites for GBM cell growth and malignancy; ⁸⁾ 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.

¹⁾

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.

²⁾

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.

³⁾

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.

⁴⁾

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.

⁵⁾

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.

⁶⁾

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.

⁷⁾

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.

⁸⁾

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.