Lsm2, a component of multiple Lsm protein complexes, is involved in RNA metabolism, such as mRNA decay, RNA splicing, and targeted RNA decay [4,5,6,7,8,9,10]. The Lsm2-8 complex binds and stabilizes the spliceosomal U6 snRNA, while Lsm2-7 associates with specific small nucleolar RNAs, contributing to their biogenesis or function [7,8,9,10]. These functions are crucial for normal cellular processes.

In disease-related research, Lsm2 has been implicated in various malignancies. In skin cutaneous melanoma (SKCM), high Lsm2 expression at both mRNA and protein levels is associated with a poor prognosis, promoting cell proliferation, migration, and invasion. Silencing Lsm2 in SKCM cells significantly inhibits these malignant behaviors [1]. In hepatocellular carcinoma (LIHC), Lsm2 is highly expressed, related to clinicopathological characteristics and poor prognosis, and knockdown of Lsm2 inhibits cell proliferation, migration, and invasion in vitro [3]. In COPD, Lsm2 is critical to club cell proliferation. Knocking down Lsm2 in vitro reduces cell viability, and knockout of Lsm2 in lungs or specifically in club cells exacerbates lung injury and inflammation caused by cigarette smoke exposure, accelerating COPD progression [2].

In conclusion, Lsm2 is essential for RNA-related cellular functions. Its role in promoting tumorigenesis in SKCM and LIHC, as well as its importance in club cell-related COPD progression, highlights the significance of Lsm2 in disease mechanisms. These findings from functional studies, including gene knockout-based research, provide insights into potential therapeutic targets for these diseases.

References:

1. Sun, Xiaofang, Zhang, Jianping, Hu, Jiayuan, Han, Qingdong, Ge, Zili. 2023. LSM2 is associated with a poor prognosis and promotes cell proliferation, migration, and invasion in skin cutaneous melanoma. In BMC medical genomics, 16, 129. doi:10.1186/s12920-023-01564-1. https://pubmed.ncbi.nlm.nih.gov/37312186/

2. Zhu, Wensi, Han, Linxiao, He, Ludan, Zhu, Qiaoliang, Zhou, Jian. 2025. Lsm2 is critical to club cell proliferation and its inhibition aggravates COPD progression. In Respiratory research, 26, 71. doi:10.1186/s12931-025-03126-8. https://pubmed.ncbi.nlm.nih.gov/40022153/

3. Qin, Peifang, Huang, Haitao, Wang, Jiahui, He, Yulin, Zhou, Yali. 2023. The mechanism of LSM2 in the progression of live hepatocellular carcinoma was analyzed based on bioinformatics. In Medical oncology (Northwood, London, England), 40, 276. doi:10.1007/s12032-023-02152-0. https://pubmed.ncbi.nlm.nih.gov/37612479/

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5. Mattout, Anna, Gaidatzis, Dimos, Padeken, Jan, Kalck, Véronique, Gasser, Susan M. 2020. LSM2-8 and XRN-2 contribute to the silencing of H3K27me3-marked genes through targeted RNA decay. In Nature cell biology, 22, 579-590. doi:10.1038/s41556-020-0504-1. https://pubmed.ncbi.nlm.nih.gov/32251399/

6. Rahman, Naimur, Sun, Jiazeng, Li, Zhili, Aryal, Uma K, Andrisani, Ourania. 2022. The cytoplasmic LSm1-7 and nuclear LSm2-8 complexes exert opposite effects on Hepatitis B virus biosynthesis and interferon responses. In Frontiers in immunology, 13, 970130. doi:10.3389/fimmu.2022.970130. https://pubmed.ncbi.nlm.nih.gov/36016928/

7. Fernandez, Cesar F, Pannone, Barbara K, Chen, Xinguo, Fuchs, Gabriele, Wolin, Sandra L. 2004. An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5. In Molecular biology of the cell, 15, 2842-52. doi:. https://pubmed.ncbi.nlm.nih.gov/15075370/

8. Montemayor, Eric J, Virta, Johanna M, Hayes, Samuel M, Brow, David A, Butcher, Samuel E. 2020. Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes. In RNA (New York, N.Y.), 26, 1400-1413. doi:10.1261/rna.075879.120. https://pubmed.ncbi.nlm.nih.gov/32518066/

9. Esteve-Bruna, David, Carrasco-López, Cristian, Blanco-Touriñán, Noel, Salinas, Julio, Alabadí, David. . Prefoldins contribute to maintaining the levels of the spliceosome LSM2-8 complex through Hsp90 in Arabidopsis. In Nucleic acids research, 48, 6280-6293. doi:10.1093/nar/gkaa354. https://pubmed.ncbi.nlm.nih.gov/32396196/

10. Roth, Allen J, Shuman, Stewart, Schwer, Beate. 2018. Defining essential elements and genetic interactions of the yeast Lsm2-8 ring and demonstration that essentiality of Lsm2-8 is bypassed via overexpression of U6 snRNA or the U6 snRNP subunit Prp24. In RNA (New York, N.Y.), 24, 853-864. doi:10.1261/rna.066175.118. https://pubmed.ncbi.nlm.nih.gov/29615482/