title: MILI, a PIWI family protein, inhibits melanoma cell migration through methylation of LINE1.
abstract: MILI, a member of the PIWI/AGO gene family, has been well documented to maintain genome integrity by transposon silencing in animal germ cells. It has been reported to be selectively expressed in precancerous stem cells (pCSCs), tumor cell lines and various malignancies. However, the underlying mechanism remains largely unclear. Here, we found that MILI is expressed in the melanoma cell line B16 but not in the highly metastatic mouse melanoma model B16BL6. Interestingly, the knockdown of MILI in B16 could activate MAGEA expression and increase the cell migration ability, whereas the overexpression of MILI in B16BL6 could inhibit MAGEA expression and decrease the cell migration ability. Further investigations showed that MILI can methylate LINE1, which is crucial for MAGEA expression and melanoma cell migration. Our results provide a novel function of MILI in melanoma metastasis and tumor progression.
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Xiuxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Bingyuan
authors.initials: B
authors.lastname: Fu
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Ruilou
authors.initials: R
authors.lastname: Zhu
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Diao
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: The School of Medicine and Model Animal Research Center, Nanjing University, Nanjing 210093, China. Electronic address: licj@nju.edu.cn.
authors.forename: Chao-Jun
authors.initials: CJ
authors.lastname: Li
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020084:Long Interspersed Nucleotide Elements; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics
chemical_list: D060565:Argonaute Proteins; D009363:Neoplasm Proteins; C448521:Piwil2 protein, mouse
keywords: LINE1; MAGEA; MILI; Melanoma