lncRNA HAR1B has potential to be a predictive marker for pazopanib therapy in patients with sarcoma

lncRNA HAR1B 有可能成为肉瘤患者帕唑帕尼治疗的预测标志物

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作者:Hideharu Yamada, Masanobu Takahashi, Munenori Watanuki, Mika Watanabe, Sakura Hiraide, Ken Saijo, Keigo Komine, Chikashi Ishioka

Abstract

Bone and soft-tissue sarcomas are rare and are highly heterogeneous mesenchymal malignancies. It is therefore challenging to acquire the clinical data of patients with specific histological subtypes of sarcoma using large clinical trials, and there is a need to further establish the diagnosis and treatment of sarcomas. The results of the current study revealed that long non-coding RNA (lncRNA) highly accelerated region 1B (HAR1B) may serve as a predictive biomarker for pazopanib treatment in bone and soft-tissue sarcomas. Using multiplex reverse transcription-quantitative PCR and microarray analyses, the results demonstrated that HAR1B and HOX transcript antisense RNA (HOTAIR) were differentially expressed in pazopanib-sensitive cells and responders. It was further revealed that small interfering RNA-knockdown of HAR1B led to an increased resistance to pazopanib in sarcoma cell lines. Gene expression profiles associated with pazopanib sensitivity included cellular molecular pathways, such as genes involved in von-Willebrand factor-related signaling. The current study demonstrated that lncRNA HAR1B expression in sarcoma cell lines affected cellular sensitivity to pazopanib in patients with sarcoma.

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