AUTHOR=Li Jun , Qin Chenjie , Wu Yicheng , Cheng Sheng , Wang Yuanqing , Chen Huijie , Chen Fangli , Chen Bingdi , Li Jutang 

TITLE=Targeting LRRC41 as a potential therapeutic approach for hepatocellular carcinoma

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1300294

DOI=10.3389/fmolb.2023.1300294

ISSN=2296-889X

ABSTRACT=Hepatocellular carcinoma (HCC) is the most common primary liver cancer, characterized by high mortality rate. In clinical practice, several makers of liver cancer, such as VEGFR1, FGFR1 and PDGFRα, were identified and their potentials as a therapeutic target were explored. However, the unsatisfied treatment results emphasized the needs of new therapeutic targets. In this study, we investigated the role of leucine-rich repeat containing 41 (LRRC41), as known as MUF1, in HCC progression and explored its potential as a therapeutic target for HCC. Through analysis of the Timer database and tissue micro-array, we confirmed that LRRC41 was over-expressed in HCC and exhibited a significant positive correlation with recurrence (P=0.000001) and metastasis (P=0.0189). Immunohistochemistry staining of human HCC tissue samples revealed significant upregulation of LRRC41, SOX9, CD44, and EPCAM, with LRRC41 showing a positive correlation with SOX9, CD44, and EPCAM expression. UALCAN database analysis indicated that LRRC41 and SOX9 contribute to poor prognosis whereas CD44 and EPCAM did not demonstrate the same significance. Furthermore, analysis of a DEN-induced HCC rat model confirmed the significantly elevated expression of LRRC41 and SOX9 in HCC and lung metastasis tissues. Drug sensitivity analysis and molecular docking targeting LRRC41 identified several FDA-approved drugs, including AZD-5363, Temsirolimus, oxiglutatione, thymopentin, deferoxamine mesylate, dermorphin, pralmoreline acetate, tetragastrin, ritonavir, leucovorin calcium pentahydrate, and pralatrexate, which may have potential antitumor effects on HCC by targeting LRRC41. Collectively, our findings highlight the role of LRRC41 overexpression in promoting HCC progression and its association with a poor prognosis. Targeting LRRC41 may hold promise as a potential therapeutic strategy for HCC.