Expression, regulation and roles of miR‐26a and MEG3 in tongue squamous cell carcinoma

Abstract

MicroRNA miR-26a and long noncoding RNA (lncRNA) MEG3 gene have been independently reported to be tumor suppressor genes in various cancers, but neither has been previously associated with tongue squamous cell carcinoma (TSCC). We report here that miR-26a and lncRNA MEG3 gene expression were both strongly reduced in TSCC compared with levels in matched nonmalignant tissues, and combined low expression levels of both miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcome in TSCC patients. Assays in the human TSCC cell lines SCC-15 and CAL27 showed that miR26a targets the DNA methyltransferase 3B transcript and that its inhibition may result in the upregulation of MEG3, providing a plausible link between the observed reduction of miR-26a and MEG3 in TSCC tissue. Furthermore, the overexpression of miR-26a or MEG3 in SCC-15 and CAL27 cells inhibited cell proliferation and cell cycle progression, and promoted cell apoptosis. Considering the poor prognostic outcomes associated with reduced miR-26a and MEG3, our findings imply that these factors likely play important antitumor effects in TSCC pathogenesis. Furthermore, they represent potential prognostic biomarkers for stratification of TSCC patients.Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well known for its high rate of proliferation and lymph nodal metastasis. 1 In clinical practice, the prediction of prognosis and planning of treatment for patients suffering from oral cancers are predominantly based on the tumor node metastasis (TNM) staging system. 2 However, in many cases of TSCC, these conventional clinical prognostic factors remain inadequate, and are unable to discriminate tumors of the same clinical stage that may have distinct clinical outcomes and different responses to the same treatments. Therefore, the identification and application of additional biomarkers into the prognostic system that better reflect the biologic diversity of TSCC and consequently predict clinical outcomes more accurately is desirable. 3 Differentially expressed genes identified from hundreds of cancer profiling studies over the last several years have yielded numerous biomarkers that have improved the subtyping, classification and diagnosis of tumors for both research and the clinic. However, the human transcriptome comprises not only large numbers of protein-coding messenger RNAs (mRNAs) but also a large set of noncoding RNAs (ncRNAs) that have structural, regulatory or unknown functions. 4 In TSCC many microRNAs (miRNAs), such as miR-195/184/ 138/21, have been shown to be dysregulated and are believed to contribute to its development and progression. [5][6][7][8] In contrast, long noncoding RNAs (lncRNAs), tentatively defined as ncRNAs more than 200 nt in length, 9 are also known to play key roles in cancer development, 10,11 and aberrant expression of lncRNAs has been functionally associated with lung, breast and prostate carcinomas. 12-14 However, whether lncRNA has relevance to TSCC biology had not been p...

lncRNA MEG3 Suppresses the Tumorigenesis of Hemangioma by Sponging miR-494 and Regulating PTEN/ PI3K/AKT Pathway

“…Accumulating data show that MEG3 is overexpressed in normal tissues [24] but downregulated in malignant tumors [10][11][12][13][14][15][16]. Low expression of MEG3 acts as an independent factor for predicting poor prognosis in cancer patients [12,15,25,26], and the downregulation of MEG3 is attributed to its promoter hypermethylation in cancer [27][28][29], and the negative modulation by DNMT1 in glioma [30].…”

“…Loss of MEG3 or its polymorphisms is associated with clinal stage, distant metastasis, unfavorable survival in patients with thyroid and ovarian carcinomas [14,15], and contributes to cell hypoxia injury [17]. MEG3 suppresses cell proliferation, cycle progression, invasion [10][11][12][13][14] and induces cell apoptosis [11], leading to the tumorigenesis [16]. These studies suggest that MEG3 may act as a tumor suppressor and a potential biomarker in cancer.…”

“…Long non-coding RNAs (lncRNAs), a group of non-coding transcripts that exceed 200 nucleotides in length, is associated with the proliferation, apoptosis and metastasis in a variety of cancers [7][8][9], of which lncRNA maternally expressed gene 3 (MEG3) has been reported to be downregulated in multiple malignancies such as nasopharyngeal carcinoma [10], tongue squamous cell carcinoma (TSCC) [11], hepatocellular carcinoma (HCC) [12], pituitary tumor [13], thyroid carcinoma [14], osteosarcoma [15], and epithelial ovarian carcinoma [16]. Loss of MEG3 or its polymorphisms is associated with clinal stage, distant metastasis, unfavorable survival in patients with thyroid and ovarian carcinomas [14,15], and contributes to cell hypoxia injury [17].…”

Novel long non-coding RNA RP11-119F7.4 as a potential biomarker for the development and progression of gastric cancer

“…Expression of the lncRNA, HOTAIR, has been correlated with tumor metastasis and poor prognosis in hepatocellular (10), pancreatic (11), breast (12) and colorectal cancer (13), and gastrointestinal stromal tumors (14). Furthermore, aberrant expression of certain lncRNAs, including ANRIL, MALAT1, H19, GAS5 and MEG3, have been reported in a number of different types of cancer (15)(16)(17)(18)(19). However, the roles of lncRNAs in gastric cancer and their association with clinicopathological characteristics in this disease remain largely unknown and therefore require further study.…”

Circulating Long Noncoding RNAs as Biomarkers for Predicting Head and Neck Squamous Cell Carcinoma

“…MALAT1 may be a promising therapeutic target for suppressing cancer progression and drug resistance [38][39][40]. Low expression levels of both miR-26a and MEG3 are an independent prognostic factor for poor clinical outcomes in tongue squamous cell carcinoma (TSCC) patients [41]. LINC00152 derived from the Gene Expression Omnibus (GEO) database might serve as a potential biomarker for the early detection and prognostic prediction of TSCC [42].…”