LYAR, also known as Ly-1 antibody reactive clone, is a cell growth-regulating nucleolar protein. It is involved in multiple biological processes and pathways. LYAR plays a role in ribosomal RNA (rRNA) synthesis, as it can recruit BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA, enhancing rRNA synthesis by altering histone acetylation [3]. It is also associated with translational control as it was identified in cytoplasmic ribosomes of male germ and cancer cells and promoted cell proliferation [6]. In addition, LYAR is implicated in the innate immune response, where it acts as a negative regulator by targeting phosphorylated interferon regulatory factor 3 (IRF3) to suppress beta interferon (IFN-β) induction [1].

In colorectal cancer (CRC), LYAR is highly expressed compared to adjacent normal tissue and is closely associated with distant metastasis. Knockdown (KD) of LYAR in CRC cells inhibits xenograft tumor metastasis in vivo. It promotes CRC cell migration and invasion by upregulating FSCN1 expression and fatty acid metabolism, as well as by activating galectin-1 expression [2,5]. In non-small cell lung cancer (NSCLC), LYAR is overexpressed, and its knockdown inhibits cell proliferation, induces G0/G1 cell cycle arrest and apoptosis [4].

In conclusion, LYAR is a multifunctional protein involved in cell growth, innate immunity, and cancer progression. Functional studies, especially those using knockdown models in cancer cells, have revealed its role in promoting tumorigenesis in CRC and NSCLC. Understanding LYAR's functions provides potential targets for treating these diseases.

References:

1. Yang, Cha, Liu, Xiaokun, Cheng, Tailang, Chen, Huanchun, Zhou, Hongbo. 2019. LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3. In Journal of virology, 93, . doi:10.1128/JVI.00769-19. https://pubmed.ncbi.nlm.nih.gov/31413131/

2. Wu, Yupeng, Zhou, Yu, Gao, Haiying, Song, Xiaoyuan, Ma, Sai. 2021. LYAR Promotes Colorectal Cancer Progression by Upregulating FSCN1 Expression and Fatty Acid Metabolism. In Oxidative medicine and cellular longevity, 2021, 9979707. doi:10.1155/2021/9979707. https://pubmed.ncbi.nlm.nih.gov/35069968/

3. Izumikawa, Keiichi, Ishikawa, Hideaki, Yoshikawa, Harunori, Min, Jinrong, Takahashi, Nobuhiro. . LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA. In Nucleic acids research, 47, 10357-10372. doi:10.1093/nar/gkz747. https://pubmed.ncbi.nlm.nih.gov/31504794/

4. Lu, Xiao-Ning, Ju, Guan-Jun, Wang, Yu-Xin, Cai, Wei, Zang, Qi-Wei. 2021. LYAR promotes the proliferation of non-small cell lung cancer and is associated with poor prognosis. In Folia histochemica et cytobiologica, 59, 282-290. doi:10.5603/FHC.a2021.0030. https://pubmed.ncbi.nlm.nih.gov/34890041/

5. Wu, Yupeng, Liu, Ming, Li, Zhuchen, Wang, Ming-Rong, Zhao, Quan. . LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression. In Oncotarget, 6, 32890-901. doi:10.18632/oncotarget.5335. https://pubmed.ncbi.nlm.nih.gov/26413750/

6. Yonezawa, Kahori, Sugihara, Yoshihiko, Oshima, Kenzi, Matsuda, Tsukasa, Nadano, Daita. 2014. Lyar, a cell growth-regulating zinc finger protein, was identified to be associated with cytoplasmic ribosomes in male germ and cancer cells. In Molecular and cellular biochemistry, 395, 221-9. doi:10.1007/s11010-014-2128-x. https://pubmed.ncbi.nlm.nih.gov/24990247/