Long Non Coding RNA MALAT1 Promotes Tumor Growth and Metastasis by inducing Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

Abstract

The prognosis of advanced oral squamous cell carcinoma (OSCC) patients remains dismal, and a better understanding of the underlying mechanisms is critical for identifying effective targets with therapeutic potential to improve the survival of patients with OSCC. This study aims to clarify the clinical and biological significance of metastasis-associated long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. We found that MALAT1 is overexpressed in OSCC tissues compared to normal oral mucosa by real-time PCR. MALAT1 served as a new prognostic factor in OSCC patients. When knockdown by small interfering RNA (siRNA) in OSCC cell lines TSCCA and Tca8113, MALAT1 was shown to be required for maintaining epithelial-mesenchymal transition (EMT) mediated cell migration and invasion. Western blot and immunofluorescence staining showed that MALAT1 knockdown significantly suppressed N-cadherin and Vimentin expression but induced E-cadherin expression in vitro. Meanwhile, both nucleus and cytoplasm levels of β-catenin and NF-κB were attenuated, while elevated MALAT1 level triggered the expression of β-catenin and NF-κB. More importantly, targeting MALAT1 inhibited TSCCA cell-induced xenograft tumor growth in vivo. Therefore, these findings provide mechanistic insight into the role of MALAT1 in regulating OSCC metastasis, suggesting that MALAT1 is an important prognostic factor and therapeutic target for OSCC.

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

“…The MALAT1 gene is highly conserved across mammals, suggesting that it may have important biological implications [9]. Evidence suggests that MALAT1 may act like an oncogene in several malignancies, including lung cancer [17, 24], pancreatic cancer [19], liver cancer [20], bladder cancer [25], prostate cancer[26], colon cancer [27, 28], renal cell carcinoma [18], and oral squamous cell carcinomas [29, 30]. Lowering MALAT1 expression in hepatocellular carcinoma cells resulted in reduced cell proliferation and colony formation [20].…”

“…For example, human maternally expressed gene 3 ( MEG3 ) could inhibit cell proliferation through both p53-dependent and p53-independent pathways [34]. MALAT1 was found to be involved in the epithelial-mesenchymal transition (EMT)-mediated metastasis in oral squamous cell carcinoma by modulating the activation of β-catenin and NF-κB pathways [29]. MALAT1 could also regulate the Wnt-β-catenin pathway by enhancing nuclear β-catenin levels and promoting c-Myc expression [18, 31].…”

MALAT1 promoted invasiveness of gastric adenocarcinoma

“…The knock down of MALAT1 altered nuclear translocation of β-catenin. MALAT1 mediated-Wnt/β-catenin regulation has reported in oral squamous, esophageal squamous cells and colorectal cancer [27–29] but did not report in gastric cancer yet.…”

Long non‐coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA‐125b/STAT3 axis

“…LncRNA UCA1 can contribute to the progression of OSCC through activating the Wnt/β‐catenin signaling pathway (Yang et al, ). In addition, MALAT1 can promote OSCC growth and metastasis via activation of Epithelial Mesenchymal Transition (EMT) signaling pathway (Zhou et al, ).…”