HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway

Abstract

Laryngeal squamous cell carcinoma (LSCC) is an aggressive and lethal malignant neoplasm with extremely poor prognoses. Accumulating evidence has indicated that preferentially expressed antigen in melanoma (PRAME) is correlated with several kinds of cancers. However, there is little direct evidence to substantiate the biological function of PRAME in LSCC. The purpose of the current study is to explore the oncogenic role of PRAME in LSCC. PRAME expression was analyzed in 57 pairs of LSCC tumor tissue samples through quantitative real-time PCR, and the correlation between PRAME and clinicopathological features was analyzed. The result indicated that PRAME was overexpressed in the LSCC patients and correlated with the TNM staging and lymphatic metastasis. The biological functions and molecular mechanism of PRAME in LSCC progression were investigated through in vitro and in vivo assays. Functional studies confirmed that PRAME facilitated the proliferation, invasion, migration, and epithelial–mesenchymal transition of LSCC cells, and PRAME also promoted tumor growth in vivo. HDAC5 was identified as an upstream regulator that can affect the expression of PRAME. Moreover, PRAME played the role at least partially by activating PI3K/AKT/mTOR pathways. The above findings elucidate that PRAME may be a valuable oncogene target, contributing to the diagnosis and therapy of LSCC.

PRAME Is a Novel Target of Tumor-Intrinsic Gas6/Axl Activation and Promotes Cancer Cell Invasion in Hepatocellular Carcinoma

“…In accordance, PRAME expression is significantly upregulated in breast cancer where it favors EMT and immunosuppression [23,24]. In a cellular model of laryngeal squamous cell carcinoma, PRAME promotes proliferation, EMT and invasion [25].…”

“…We particularly focused on PRAME as its expression associates with EMT in breast cancer and laryngeal squamous cell carcinoma [23][24][25]. Furthermore, the CTA is linked to an unfavorable prognosis in HCC as well as an increased risk for hepatic metastasis and hepatic recurrence in gastric cancer [41,57].…”

“…As CTAs have been linked to tumor progression by modulating epithelial cell plasticity [21][22][23][24][25]46], we analyzed whether PRAME contributes to an EMT phenotype in liver cancer. Therefore, we stratified publicly available HCC patient datasets according to PRAME expression and identified transcripts upregulated in PRAME-high patients including CTNND2, DLK1, KRT19, EPCAM, DKK1, AFP, MMP7 (Figure 2A).…”

N6-methyladenosine methylation in kidney injury

“…HDAC5, a member of the histone deacetylase family, has been identified to be associated with the EMT process in some cancer cells [ 124 , 125 ]. PI3K/AKT signaling pathway-regulated HDAC5 was also revealed to facilitate the EMT process in high-glucose-stimulated HK-2 cells [ 53 ].…”

Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes

“…PRAME is a transcriptional repressor of retinoic acid signaling and thereby regulates cellular growth, differentiation, and apoptosis [ 2 ]. Moreover, it has been implicated in the promotion of invasion, metastasis, epithelial-to-mesenchymal transition, and genomic instability in a number of cancers [ 3 , 4 , 5 , 6 , 7 ]. Notably, cytotoxic T lymphocytes have been shown to effectively target PRAME-expressing cancer cells [ 8 , 9 ].…”