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Aberrant HGF-MET signaling activation via interactions with surrounding stromal cells in tumor microenvironment plays significant roles in malignant tumor progression. However, extracellular proteolytic regulation of HGF activation which is influenced by the tumor microenvironment and its consequential effects on melanoma malignancy remain uncharacterized. In this study we identified SPINT2: a proteolytic inhibitor of hepatocyte growth factor activator (HGFA), which plays a significant role in the suppression of the HGF-MET pathway and malignant melanoma progression. SPINT2 expression is significantly lower in metastatic melanoma tissues compared to those in early stage primary melanomas which also corresponded with DNA methylation levels isolated from tissue samples. Treatment with the DNA hypomethylating agent decitabine in cultured melanoma cells induced transcriptional reactivation of SPINT2, suggesting that this gene is epigenetically silenced in malignant melanomas. Furthermore, we show that ectopically expressed SPINT2 in melanoma cells inhibits HGF induced MET-AKT signaling pathway and decreases malignant phenotype potential such as cell motility, and invasive growth of melanoma cells. These results suggest that SPINT2 is associated with tumor suppressive functions in melanoma by inhibiting an extracellular signal regulator of HGF which is typically activated by tumor-stromal interactions. These findings indicate that epigenetic impairment of the tightly regulated cytokine-receptor communications in tumor microenvironment may contribute to malignant tumor progression.

Overview of TikTok's most viewed dermatologic content and assessment of its reliabilityTo the Editor: Around 80% of people seek medical information online, and #45% report that social media influences their decisions to seek medical care. 1,2 With [2 billion total downloads, TikTok is the world's fastest growing social media platform. This popular app allows users to create and share short videos on numerous topics, including health care. Previous studies have analyzed the dermatologic content posted on Instagram, Twitter, and YouTube. 3 This study is the first to characterize the content, sources, and reliability of the most popular dermatology videos on TikTok.Based on the National Ambulatory Medical Care Survey, we generated a list of the top 20 most commonly diagnosed dermatologic conditions. 4 On September 18, 2020, these diagnoses were queried as hashtags on TikTok, and the 8 diagnoses with the most videos were evaluated (Table I). The top 25 videos per diagnosis were identified based on engagement, a TikTok metric based on views, likes, comments, and shares. Videos unrelated to dermatology, paid advertisements, and non-English videos were excluded. Two investigators classified the remaining videos into $1 categories based on content. Interrater reliability was calculated using Cohen . Educational videos were subcategorized and compared with American Academy of Dermatology (AAD) guidelines to determine reliability. 5 Four board-certified dermatologists reviewed content assessment. The identities of content creators were confirmed through biographic information on TikTok or other linked social media platforms; board-certified dermatologists were confirmed through the AAD. Identity confirmation required $2 sources of congruent biographic information. Statistical analysis was performed using the z score test for 2 population proportions. P \.05 was considered statistically significant.Of the 200 videos identified, 171 were included. These videos amassed [521 million views. Videos were most often related to patient experiences/ testimonies, followed by education, clinical demonstrations/live procedures, and product reviews/nonpaid advertisements (Table I). Cohen yielded 0.988, showing excellent interrater reliability on content categorization. Content creators were most commonly patients (48.0%), board-certified dermatologists (25.8%), and estheticians (4.8%) (Table I). Board-certified dermatologists were the main source of educational videos (41.3%), adhering to AAD guidelines 96.8% of the time (Table II).Percentages are based on 171 total videos. *Videos were classified into $1 categories. y Defined as information about prevention, cause, diagnosis, and treatment of skin disease. z Defined as advice on skin appearance, and use/application of beauty and skin care products.x Makeup artists, barbers, relatives of patients, and unidentified posters.

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Expanded non-coding RNA repeats of CUG and CCUG are the underlying genetic causes for myotonic dystrophy type 1 (DM1) and type 2 (DM2), respectively. A gain-of-function of these pathogenic repeat expansions is mediated at least in part by their abnormal interactions with RNA-binding proteins such as MBNL1 and resultant loss of activity of these proteins. To study pathogenic mechanisms of CCUG-repeat expansions in an animal model, we created a fly model of DM2 that expresses pure, uninterrupted CCUG-repeat expansions ranging from 16 to 720 repeats in length. We show that this fly model for DM2 recapitulates key features of human DM2 including RNA repeat-induced toxicity, ribonuclear foci formation and changes in alternative splicing. Interestingly, expression of two isoforms of MBNL1, MBNL135 and MBNL140, leads to cleavage and concurrent upregulation of the levels of the RNA-repeat transcripts, with MBNL140 having more significant effects than MBNL135. This property is shared with a fly CUG-repeat expansion model. Our results suggest a novel mechanism for interaction between the pathogenic RNA repeat expansions of myotonic dystrophy and MBNL1.

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