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

Abstract

Oral squamous cell carcinoma (OSCC), as the most common type of oral cancer, is responsible for almost 3% of all malignant tumors worldwide. Non-coding RNAs such as lncRNAs and microRNAs have been involved in many cancers including OSCC. Recently, lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) has been reported to play an oncogenic role in OSCC metastasis. However, the underlying mechanism of MALAT1 in regulating OSCC progression remains unclear. The aim of this study was to investigate the specific role of MALAT1 in OSCC development. It was observed that MALAT1 was upregulated in OSCC cell lines. Inhibition of MALAT1 can prevent OSCC proliferation while overexpressing MALAT1 promoted OSCC progression. In addition, bioinformatics search was used to identify that miR-125b was a direct target of MALAT1, which indicated a negative correlation between MALAT1 and miR-125b. Besides these, STAT3 was predicted as a binding target of miR-125b in OSCC. Overexpression of MALAT1 was able to suppress the tumor inhibitory effect of miR-125b mimics via upregulating STAT3. Moreover, the function of MALAT1 in OSCC development was further investigated by using in vivo assays. The established nude mice models revealed that downregulated MALAT1 greatly inhibited OSCC tumor growth and reversely upregualated MALAT1 promoted OSCC development via miR-125b/STAT3 axis, respectively. In conclusion, MALAT1 can function as a competing endogenous RNA (ceRNA) to modulate STAT3 expression by absorbing miR-125b in OSCC and could be used as a novel therapeutic target in OSCC diagnosis and treatment.

Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma

“…Meng Zhuang et al demonstrated that MALAT1 might be a potential ceRNA by sponging miR-106b-5p in colorectal cancer. Accordingly, it promotes invasion and metastasis by regulating miR-106b-5p, which is in agreement with other authors' findings [20,32,41,42]. In hepatocellular carcinoma, MALAT1 is up-regulated and acts as a proto-oncogene via the activation of the Wnt pathway and induction of the oncogenic splicing factor SRSF [7].…”

MALAT1 induces osteosarcoma progression by targeting miR‐206/CDK9 axis

“…targeting miR-125b and signal transducer and activator of transcription 3 (Chang & Hu, 2017). MALAT1 can promote breast cancer development by inhibiting miR-129-5p (Zuo, Li, Zhou, Ma, & Fu, 2017).…”

World Workshop on Oral Medicine VII: Functional pathways involving differentially expressed lncRNAs in oral squamous cell carcinoma

“…In vitro, MALAT1 was found to act as a sponge downregulating miR‐125b, which conversely led to a significant upregulation of STAT3 thus favouring cell proliferation in colony formation assays. In addition, when assessing tumour size recorded in a time‐dependent manner in a xenograft model, the inhibition of MALAT1 was found to significantly inhibit tumour growth, while upregulations had an opposite effect (Chang & Hu, ).…”