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Thomas Flaig, MD

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Could a HOTAIR-Related RNA Signaling Pathway Be the Key to Cachexia Relief?

By: Joshua Swore, PhD
Posted: Tuesday, February 14, 2023

Hox transcript antisense intergenic RNA (HOTAIR) signaling pathway has been identified as a new potential therapeutic target for cisplatin-induced cachexia in bladder cancer, according to an article published in the Journal of Biomedical Science. “Remarkably, cachexia rather than tumor burden is responsible for approximately one-third of cancer-related deaths,” said Chao-Liang Wu, PhD, of the National Cheng Kung University, Taiwan, and colleagues, “Cachexia negatively affects patients’ quality of life and physical function and is associated with poor prognosis and survival. While there has been great progress in understanding the pathophysiology of cachexia, no specific treatments or interventions are currently available.”

The researchers used real-time polymerase chain reaction to identify a potential correlation in the expression patterns of prothymosin alpha (ProT) and HOTAIR. This analysis revealed that the expression levels of ProT and HOTAIR transcripts were higher in tumors than in healthy adjacent cells. Immunoblot assays were used to assess the levels of genese phospho-EGFR, EGFR, phopho-NF-κB, and NF-κB within cancer cells.

The authors treated bladder cancer cells with cisplatin and identified an increase in EGFR and NF-κB activation. ProT and HOTAIR were also upregulated during this treatment. This led the authors to identify that the expression of ProT seemed to regulate the expression of HOTAIR. However, by inhibiting NF-κB, the authors were able to reduce HOTAIR overexpression. The group further noted that HOTAIR had a direct influence on cell replication, where overexpression increased and knockdown decreased cell proliferation.

The authors used mice with MBT-2 bladder tumors to identify HOTAIR’s role in cisplatin-induced cancer cachexia. By knocking down the expression of HOTAIR in this model, the group observed reduced symptoms of cachexia.

Disclosure: The study authors reported no conflicts of interest.


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