LncRNA MEG3 suppresses migration and promotes apoptosis by sponging miR‐548d‐3p to modulate JAK–STAT pathway in oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a lethal malignancy and its prognosis remains dismal. Thus, a deeper understanding of the mechanisms is needed to provide a new insight for new therapies. It has been reported that long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) was downregulated in OSCC tissues, however, its functional mechanism remains uncertain. Here, we found that the overexpression of MEG3 suppressed migration and promoted apoptosis in OSCC cell lines, while inhibition of MEG3 exhibited opposite effect. We also found that MEG3 could effectively sponge miR‐548d‐3p and decrease its expression level. Moreover, miR‐548d‐3p repressed the expression of SOCS5 and SOCS6 through binding their 3’UTR, thereby modulating the JAK–STAT signaling pathway and functioning as an oncogene in OSCC cells. Importantly, overexpression of MEG3 enhanced the expression of SOCS5 and SOCS6 to regulate JAK–STAT pathway, whereas miR‐548d‐3p overexpression decreased the effects of MEG3 on levels of SOCS5/SOCS6. Furthermore, upregulated expression of miR‐548d‐3p could abrogate the effect of MEG3 overexpression on migration and apoptosis in OSCC cell lines. In addition, the overexpression of MEG3 inhibited tumor migration and facilitated apoptosis in vivo. Together, our results revealed that MEG3 could modulate JAK–STAT pathway via miR‐548d‐3p/SOCS5/SOCS6 to suppresses migration and promote apoptosis in OSCC. Our research indexed a new functional mechanism of MEG3 in OSCC, and this mechanism may be a potential prognostic factor and therapeutic target. © 2019 IUBMB Life, 2019

lncRNA SNHG5 promotes cell proliferation, migration and invasion in oral squamous cell carcinoma by sponging miR‑655‑3p/FZD4 axis

“…Recently, the important roles of lncRNAs have been widely investigated in the progression of OSCC. Previous studies have indicated shown that lncRNA can play an inhibitory or carcinogenic effect in OSCC (20,21). In this study, upregulation of lncRNA SNHG5 was detected in OSCC.…”

Long non‑coding RNA MEG3 suppresses epithelial‑to‑mesenchymal transition by inhibiting the PSAT1‑dependent GSK‑3β/Snail signaling pathway in esophageal squamous cell carcinoma

“…MEG3 has been proposed to play a biological role in various diseases, particularly cancer. Recent studies demonstrated that MEG3 is involved in the regulation of cancer-related pathways, and contributes to cell proliferation, metabolism, tumor progression and metastasis (9)(10)(11)(12)(13)(14). In the present study, the expression and role of MEG3 in ESCC were assessed, and the mechanisms underlying its activity were investigated.…”

“…The lncRNA maternally expressed gene 3 (MEG3) is widely expressed in a variety of normal tissues. MEG3 has been identified as a tumor suppressor and is expressed at lower levels in diverse types of cancer (9)(10)(11)(12)(13). However, whether MEG3 is involved in the EMT process of ESCC remains elusive.…”

p53‐induced long non‐coding RNA PGM5‐AS1 inhibits the progression of esophageal squamous cell carcinoma through regulating miR‐466/PTEN axis

“…It has been well documented that lncRNA plays a critical role in the initiation, development, and progression of human cancer by functioning as an endogenous microRNA (miRNA) sponge . For example, LINC00336 was reported to facilitate lung cancer progression via sponging miR‐6,852; LncRNA SNHG6 directly bound to miR‐26a/b and miR‐214 to promote the growth and metastasis of colorectal cancer; LncRNA MEG3 was proposed to suppress migration and promote apoptosis of oral squamous cell carcinoma cells by effectively sponging miR‐548d‐3p . Likewise, several lncRNAs have also been identified to be involved in ESCC tumorigenesis, such as HOTTIP, EGFR‐AS1, FAL1, and LINC01503 .…”

“…7,8 For example, LINC00336 was reported to facilitate lung cancer progression via sponging miR-6,852 9 ; LncRNA SNHG6 directly bound to miR-26a/b and miR-214 to promote the growth and metastasis of colorectal cancer 10 ; LncRNA MEG3 was proposed to suppress migration and promote apoptosis of oral squamous cell carcinoma cells by effectively sponging miR-548d-3p. 11 Likewise, several lncRNAs have also been identified to be involved in ESCC tumorigenesis, such as HOTTIP, 12 EGFR-AS1, 13 FAL1, 14 and LINC01503. 15 Thus, although a small fraction of lncRNAs in cancer have been well delineated, the roles of many members in this class are still unknown, which needs to be further elucidated.…”