Loss of miR-1469 expression mediates melanoma cell migration and invasion.

Mallory J Divincenzo,Zoe Barricklow,Emily Schwarz,Maribelle Moufawad,J Harrison Howard,Lianbo Yu,Catherine Chung,Alejandro A Gru,William E Carson,Klaus Roemer

doi:10.1371/journal.pone.0256629

Mallory J Divincenzo, Zoe Barricklow + Show 8 more

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https://doi.org/10.1371/journal.pone.0256629

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Abstract

Tumor ulceration is considered one of the most prognostically significant findings in primary cutaneous melanoma, associated with decreased disease-free and overall survival. However, the unique features associated with ulcerated melanoma that contribute to a poor prognosis in affected patients remain poorly defined. microRNAs are small, non-coding RNAs that function to inhibit expression of specific gene targets, therefore altering the functions of cells in which they are expressed. miR-1469 is a novel miR with significantly decreased expression in ulcerated melanoma tissue relative to non-ulcerated tumors. We hypothesized that loss of miR-1469 expression in melanoma contributes to altered tumor cell functions mediating disease progression. Transfection of a miR-1469 mimic resulted in a significant reduction in the migratory and invasive capacity of the CHL1 and MEL39 melanoma cell lines (>58.1% reduction, p < 0.0332), as well as the invasive capacity of the A375 melanoma cell line (>50% reduction, p < 0.0021). Expression of myeloid cell leukemia-1 (MCL1), a miR-1469 target gene, was reduced in the A375 and MEL39 cell lines by immunoblot. No significant differences in viability, resistance to apoptotic stimuli, or proliferation were observed following transfection. These findings together demonstrate how migration and invasion are specific functions through which miR-1469 expression in melanoma cells can contribute to the differences in disease progression associated with tumor ulceration.

Highlights

Melanoma is the leading cause of skin cancer-related death, associated with nearly 7,000 deaths in 2020 in the United States alone [1]
Results miR-1469 expression is significantly decreased in ulcerated cutaneous melanoma relative to non-ulcerated cutaneous melanoma miR-1469 expression was found to be decreased in a group of ulcerated primary cutaneous melanoma samples relative to non-ulcerated cutaneous melanoma by Nanostring miR analysis (1.34 fold decrease, p = 0.0482, Fig 1A)
As miR-1469 dysregulation was found to be a feature associated with ulcerated primary cutaneous melanoma and limited studies have explored its role in cancer, an in vitro functional assessment of miR-1469 expression was performed using melanoma cell lines

Summary

Introduction

Melanoma is the leading cause of skin cancer-related death, associated with nearly 7,000 deaths in 2020 in the United States alone [1]. Cutaneous melanoma can sometimes present with ulceration of the tumor surface. Tumor ulceration is defined as the full thickness loss of epidermis overlying the tumor to the level of the basement membrane, with evidence of a host inflammatory response and associated thinning, effacement, or reactive hyperplasia of the adjacent epidermis [2]. Tumor ulceration has been correlated with both decreased disease-free.

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