LMO3, or LIM domain only 3, is a transcription co-factor that interacts with transcription factors to regulate target genes involved in embryonic development [3,7]. It has been implicated in various biological processes and disease conditions, playing important roles in adipocyte metabolism, cancer development, and neurodevelopment.

In obesity, LMO3 expression in visceral adipose tissue significantly improves insulin sensitivity, healthy adipose tissue expansion, and adiponectin secretion. It increases glucose uptake, mitochondrial oxidative capacity, and fatty acid oxidation in adipocytes, acting through the induction of the PPARγ coregulator Ncoa1 [1]. In prostate cancer (PCa), LMO3 expression is significantly decreased, and low expression is associated with poor prognosis, being engaged in the extracellular matrix and immune response [2]. In papillary thyroid carcinoma (PTC), knockdown of LMO3 represses cell proliferation, promotes apoptosis, and retards cell migration and invasion, regulating LIMK1-mediated cofilin and the β-catenin pathway [3]. In glioma, lncRNA SNHG6 promotes LMO3 expression by sponging miR-543, and LMO3 silencing inhibits glioma cell progression [5]. In Ewing sarcoma at relapse, the newly identified LMO3-BORCS5 fusion oncogene drives tumor progression [6]. In gastric cancer, LMO3 promotes cell invasion and proliferation through Akt-mTOR and Akt-GSK3β signaling [8]. In pancreatic cancer, reduced LMO3 expression is associated with a more aggressive basal-like/squamous subtype, and LMO3 overexpression inhibits cell proliferation and migration, with glycerol 3-phosphate metabolism being involved [9]. In the nervous system, Lmo3 deficiency in mice is associated with alterations in mood-related behaviors, impairments in learned fear, and a depression-biased amygdala transcriptome [4]. Also, Lmo3 is required for the development of medial ganglionic eminence derived neurons in the external globus pallidus [10].

In conclusion, LMO3 plays diverse and crucial roles in metabolism, cancer, and neurodevelopment. Studies using gene-knockout models, such as Lmo3-null mice, have been instrumental in revealing its functions in these areas, offering insights into potential therapeutic targets for obesity-related metabolic disorders, various cancers, and neurological conditions [1-10].

References:

1. Wagner, Gabriel, Fenzl, Anna, Lindroos-Christensen, Josefine, Esterbauer, Harald, Bilban, Martin. 2021. LMO3 reprograms visceral adipocyte metabolism during obesity. In Journal of molecular medicine (Berlin, Germany), 99, 1151-1171. doi:10.1007/s00109-021-02089-9. https://pubmed.ncbi.nlm.nih.gov/34018016/

2. Xu, Wenchao, Sun, Taotao, Wang, Jiaxin, Liu, Jihong, Jiang, Hongyang. 2022. LMO3 downregulation in PCa: A prospective biomarker associated with immune infiltration. In Frontiers in genetics, 13, 945151. doi:10.3389/fgene.2022.945151. https://pubmed.ncbi.nlm.nih.gov/36199576/

3. Ling, Zeyi, Long, Xiaoli, Wu, Ying, Li, Jie, Feng, Mingliang. 2022. LMO3 promotes proliferation and metastasis of papillary thyroid carcinoma cells by regulating LIMK1-mediated cofilin and the β-catenin pathway. In Open medicine (Warsaw, Poland), 17, 453-462. doi:10.1515/med-2022-0419. https://pubmed.ncbi.nlm.nih.gov/35350839/

4. Reisinger, Sonali N, Bilban, Martin, Stojanovic, Tamara, Boehm, Stefan, Pollak, Daniela D. 2019. Lmo3 deficiency in the mouse is associated with alterations in mood-related behaviors and a depression-biased amygdala transcriptome. In Psychoneuroendocrinology, 111, 104480. doi:10.1016/j.psyneuen.2019.104480. https://pubmed.ncbi.nlm.nih.gov/31707294/

5. Zhang, Yin, An, Jiayin, Pei, Yuchun. 2020. LncRNA SNHG6 promotes LMO3 expression by sponging miR-543 in glioma. In Molecular and cellular biochemistry, 472, 9-17. doi:10.1007/s11010-020-03772-0. https://pubmed.ncbi.nlm.nih.gov/32613482/

6. Dupain, Célia, Gracia, Céline, Harttrampf, Anne C, Geoerger, Birgit, Massaad-Massade, Liliane. 2019. Newly identified LMO3-BORCS5 fusion oncogene in Ewing sarcoma at relapse is a driver of tumor progression. In Oncogene, 38, 7200-7215. doi:10.1038/s41388-019-0914-3. https://pubmed.ncbi.nlm.nih.gov/31488873/

7. Isogai, Eriko, Okumura, Kazuhiro, Saito, Megumi, Nagase, Hiroki, Wakabayashi, Yuichi. 2015. Oncogenic Lmo3 cooperates with Hen2 to induce hydrocephalus in mice. In Experimental animals, 64, 407-14. doi:10.1538/expanim.15-0026. https://pubmed.ncbi.nlm.nih.gov/26156403/

8. Qiu, Yan-Song, Jiang, Ning-Ning, Zhou, Yan, Gong, Hong-Yan, Liao, Guang-Jun. 2018. LMO3 promotes gastric cancer cell invasion and proliferation through Akt-mTOR and Akt-GSK3β signaling. In International journal of molecular medicine, 41, 2755-2763. doi:10.3892/ijmm.2018.3476. https://pubmed.ncbi.nlm.nih.gov/29436606/

9. Ohara, Yuuki, Craig, Amanda J, Liu, Huaitian, Ambs, Stefan, Hussain, S Perwez. . LMO3 is a suppressor of the basal-like/squamous subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism. In Carcinogenesis, 45, 475-486. doi:10.1093/carcin/bgae011. https://pubmed.ncbi.nlm.nih.gov/38366633/

10. Biswas, Shiona, Chan, C Savio, Rubenstein, John L R, Gan, Lin. 2023. The transcription regulator Lmo3 is required for the development of medial ganglionic eminence derived neurons in the external globus pallidus. In Developmental biology, 503, 10-24. doi:10.1016/j.ydbio.2023.07.007. https://pubmed.ncbi.nlm.nih.gov/37532091/