Elfn1, extracellular leucine rich repeat and fibronectin type III domain containing 1, is a single-pass transmembrane protein. In the central nervous system, it is a universal binding partner of metabotropic glutamate receptors (mGluRs), and its deficiency is linked to the pathogenesis of neurological and neuropsychiatric diseases. A 2024 study also proposed its involvement in cell-extracellular matrix (ECM) attachment, suggesting functions beyond the nervous system [4].

Multiple studies focus on its antisense RNA, ELFN1-AS1. In various cancers like colorectal, gastric, ovarian, colon, and retinoblastoma, ELFN1-AS1 acts as an oncogene. For example, in colorectal cancer, ELFN1-AS1, via the ELFN1-AS1/EZH2/DNMT3a axis, downregulates MEIS1, promoting tumorigenesis and oxaliplatin resistance [1]. In gastric cancer, it upregulates TRIM29 by suppressing miR-211-3p, advancing cancer progression [2]. In ovarian cancer, it accelerates cell proliferation, invasion, and migration through the miR-497-3p/CLDN4 axis [5]. In colon cancer, it enhances malignancy by targeting miR-4270 to upregulate AURKB [6]. In retinoblastoma, it promotes growth and invasion via the miR-4270/SBK1 axis [3]. Also, in colorectal cancer, ELFN1-AS1 promotes GDF15-mediated immune escape from NK cells by facilitating GCN5 and SND1 association [7], and promotes cancer cell proliferation, migration, invasion, and suppresses apoptosis by enhancing G6PD activity [8].

In conclusion, while Elfn1 has important functions in the nervous system and potentially in connective tissue related to the ECM, its antisense RNA, ELFN1-AS1, is significantly involved in promoting tumorigenesis, cancer cell proliferation, invasion, migration, drug resistance, and immune escape in multiple cancer types. Research on Elfn1 and ELFN1-AS1 helps in understanding cancer mechanisms and could potentially lead to new therapeutic strategies.

References:

1. Li, Yimin, Gan, Yaqi, Liu, Jiaxin, Shu, Guang, Yin, Gang. 2022. Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer. In Signal transduction and targeted therapy, 7, 87. doi:10.1038/s41392-022-00902-6. https://pubmed.ncbi.nlm.nih.gov/35351858/

2. Huang, Jinxi, Yuan, Weiwei, Chen, Beibei, Li, Gaofeng, Chen, Xiaobing. . lncRNA ELFN1-AS1 upregulates TRIM29 by suppressing miR-211-3p to promote gastric cancer progression. In Acta biochimica et biophysica Sinica, 55, 484-497. doi:10.3724/abbs.2023023. https://pubmed.ncbi.nlm.nih.gov/36876422/

3. Feng, Wanguo, Zhu, Ruixi, Ma, Junlong, Song, Han. 2021. LncRNA ELFN1-AS1 Promotes Retinoblastoma Growth and Invasion via Regulating miR-4270/SBK1 Axis. In Cancer management and research, 13, 1067-1073. doi:10.2147/CMAR.S281536. https://pubmed.ncbi.nlm.nih.gov/33574704/

4. Ayhan, Selda, Dursun, Ali. 2024. ELFN1 is a new extracellular matrix (ECM)-associated protein. In Life sciences, 352, 122900. doi:10.1016/j.lfs.2024.122900. https://pubmed.ncbi.nlm.nih.gov/38986898/

5. Jie, Youkun, Ye, Lu, Chen, He, He, Wenfeng, Fu, Yonghui. . ELFN1-AS1 accelerates cell proliferation, invasion and migration via regulating miR-497-3p/CLDN4 axis in ovarian cancer. In Bioengineered, 11, 872-882. doi:10.1080/21655979.2020.1797281. https://pubmed.ncbi.nlm.nih.gov/32779991/

6. Peng, Shuangqin, Luo, Yanjun, Chen, Lijuan, Dai, Kang, Wang, Qin. 2022. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB. In Open medicine (Warsaw, Poland), 17, 1999-2012. doi:10.1515/med-2022-0582. https://pubmed.ncbi.nlm.nih.gov/36561847/

7. Han, Bin, He, Jinsong, Chen, Qing, Feng, Dan, Ma, Daiyuan. 2023. ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association. In Discover oncology, 14, 56. doi:10.1007/s12672-023-00675-6. https://pubmed.ncbi.nlm.nih.gov/37147528/

8. Wu, Fahong, Zhang, Wei, Wei, Hangzhi, Leng, Guangxian, Zhang, Youcheng. . lncRNA ELFN1-AS1 promotes proliferation, migration and invasion and suppresses apoptosis in colorectal cancer cells by enhancing G6PD activity. In Acta biochimica et biophysica Sinica, 55, 649-660. doi:10.3724/abbs.2023010. https://pubmed.ncbi.nlm.nih.gov/36786074/