LNMAT1 Promotes Invasion-Metastasis Cascade in Malignant Melanoma by Epigenetically Suppressing CADM1 Expression
Authors: Xin Mu
Yan Zhou
Rui Ge
Xiang Zhang
Lijuan Wang
Kuanhou Mou
Dan Han
Journal: Frontiers in Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: CADM1; EZH2; LNMAT1; invasion-metastasis cascade; malignant melanoma.
Affiliations: Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Department of Clinical Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Abstract:  The invasion-metastasis cascade is one of the most important factors relating to poor survival and prognosis of malignant melanoma (MM) patients. Long non-coding RNA lymph node metastasis associated transcript 1 (LNMAT1) is a key regulator in lymph node metastasis of multiple cancer types, but the roles and underlying mechanisms of LNMAT1 in the invasion-metastasis cascade of MM remain unclear. In the present study, we aimed to investigate the expression and function of LNMAT1 in MM. Here, we found that LNMAT1 was upregulated in MM tissues and cells, and its expression levels were further enhanced in MM patients with lymph node metastasis and metastatic MM cells. Using loss-of-function assays, we found that LNMAT1 promoted cell migration and invasion and lung metastasis in MM in vitro and in vivo. Moreover, we found that cell adhesion molecule 1 (CADM1), the established tumor suppressor in MM, was the downstream target of LNMAT1. Mechanistically, LNMAT1 epigenetically suppressed CADM1 expression by recruiting EZH2, the key regulator of trimethylation of histone H3 at lysine 27 (H3K27me3), to the CADM1 promoter, resulting in transcriptional inhibition of CADM1. Lastly, rescue assays demonstrated that LNMAT1 promoted cell migration and invasion of MM by suppressing CADM1 expression. Our findings elucidate a new mechanism for LNMAT1-mediated invasion-metastasis cascade in MM and suggest that LNMAT1 may be a new therapeutic target and prognostic predictor for MM. 

Retracted: No

PubPeer comments:
 Of great concern, an image in Figure 4B seems to also overlap with an image in a different paper (after rotation) where it is described differently. The last author seems to be the same on both papers and they were essentially submitted simultaneously to the two different journals. That other paper: Supplemental Figure 3A and 3B, International Journal of Oncology (2019), DOI: 10.3892 ijo.2019.4848, Received April 12, 2019, https: pubpeer.com publications 46ED98DFE1ED978294C50AADA8FDBC#6 *** ![file] , 
 An image in Figure 2D and 4E appear to overlap, with different brightness. Difficult to understand how this transformation could occur merely as an error during figure assembly. *** ![file] *** This work was supported by the National Natural Science Foundation of China (No. 81802935) and Foundation of the First Affiliated Hospital of Xiu2019an Jiaotong University (grant number: 2018MS-04). , 
 Dear Actinopolyspora biskrensis Thank you for reminding us of this huge mistake. Because the experiments of these two articles were carried out at almost the same time, some errors might occur when analyzing the experimental data. We will try our best to find the possible reasons. If necessary, we will make corrections. IF our mistakes affect the academic atmosphere, we can even retract the manuscript without hesitation. Yours sincerely Wang Lijuan , 
 **Carefully observe that in Figure 2G, the mouse shown by the red arrow is actually the same mouse**. ![file] ![file] ![file] , 
 ![file] Dear Ageratina aromatica: Thank you for your interest to our study. From the original data, we could see the present image were from different shooting during in vivo image. The mistake of repeated pictures was caused by incaution of compose type. Though we have contacted the journal to want have the chance to submitted a correction, we still have not received the reply. Yours sincerely Wang Lijuan ,