Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by targeting SOX2 in hepatocellular carcinoma

Zhang, Di; Jiang, Jiong; Liu, Dong

doi:10.3892/or.2016.5273

Cited by 36 publications

(28 citation statements)

References 30 publications

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“…This result was in consistence with others. For instance, attenuated miR-638-SOX2 axis was reported to promote the invasion by inducing epithelialmesenchymal transition in non-small-cell lung cancer [21], colorectal carcinoma [36], hepatocellular carcinoma [22]. Remarkably, Vanner and Boumahdi et al revealed SOX2 was important in regulating cancer stem-like cells [30,37].…”

Section: Figure 5: Knockdown Of Sox2 Antagonized the Pro-invasion Andmentioning

confidence: 99%

miR-488 acts as a tumor suppressor gene in gastric cancer

Zhao

et al. 2016

Tumor Biol.

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Gastric cancer is one of the major causes of cancer mortality. Several microRNAs play a role in the tumor growth and invasion. However, the underlying molecular mechanism remains poorly understood. We detected the miR-638 expression levels in tumor samples and adjacent noncancerous tissues from 68 patients with gastric cancer as well as in the gastric cancer cell line SGC-7901 and SC-M1. The cell cycle was analyzed by flow cytometry, cell proliferation was observed by CCK-8 assay and cell invasion was detected using Transwell assay. MiR-638 was down-regulated in human GC tissues and its expression level was negatively correlated to TNM stage and lymph metastasis. In the cell lines, aberrant expression of miR-638 was related to the cell proliferation, cell cycle and invasion. We also found that SOX2 had a negative correlation with miR-638 in GC tissues, and miR-638 overexpression could decrease SOX2 expression level by directly binding the 3'-UTR of SOX2. in vitro, downregulating SOX2 by siRNA could counteract the effect of miR-638 inhibitor on GC cells proliferation and invasion. Our results demonstrate that miR-638 may play a pivotal role in the growth and invasion of GC.

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Section: Figure 5: Knockdown Of Sox2 Antagonized the Pro-invasion Andmentioning

confidence: 99%

miR-488 acts as a tumor suppressor gene in gastric cancer

Zhao

et al. 2016

Tumor Biol.

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“…miR-638 is upregulated and acts as a tumor promoting miRNA in prostate cancer (7), esophageal carcinoma (9), breast cancer (9) and melanoma (10). Nevertheless, miR-638 was demonstrated to be downregulated and to function as a tumor suppressive miRNA in gastric (8,11), cervical (12) and breast cancer (13), and hepatocellular carcinoma (14). The methylation status, expression level and biological roles of miR-638 have not been investigated in Ec.…”

Section: Introductionmentioning

confidence: 99%

Methylation‑associated silencing of miR‑638 promotes endometrial carcinoma progression by targeting MEF2C

Liang

Shan

et al. 2020

Int J Mol Med

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Promoter methylation-associated silencing of cancer-associated microRNAs (miRNAs) is a common epigenetic mechanism during tumorigenesis in various types of human cancer. However, this has not been comprehensively examined in endometrial carcinoma (Ec). In the present study, an miRNA microarray consisting of 1,347 common human miRNAs was used to select potential tumor suppressive miRNAs that were hyper-methylated in Ec. This led to the identification of miR-638, miR-210 and miR-3665. The methylation status of miR-638 was examined by bisulfite sequencing polymerase chain reaction and miR-638 expression was measured by TaqMan miRNA assays. Ec cell lines transfected with vectors overexpressing miR-638, its target gene myocyte enhancer factor 2c (MEF2c) or both, were constructed. dual-luciferase reporter assays, a xenograft mouse model and rescue experiments were designed to study miR-638 and its target gene MEF2C. The results indicated that the promoter region of miR-638 was highly methylated and the expression of miR-638 was significantly downregulated in cancerous tissues from 42 patients with Ec who underwent surgical resection. Additionally, a low expression of miR-638 was significantly associated with advanced Federation of Gynecology and Obstetrics stage and was demonstrated to indicate shorter disease-free survival. Functional studies indicated that the overexpression of miR-638 in EC cell lines inhibited in vitro tumor progression and in vivo tumorigenicity. MEF2C was verified as a direct target of miR-638 and was demonstrated to mediate the tumor-suppressive function of miR-638 in EC.

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“…In line with this, several studies have reported that miR-638 suppressed cell invasion, proliferation and epithelial-mesenchymal transition by downregulating SOX2 gene expression in non-small cell lung cancer (NSCLC) and colorectal carcinoma cells (27,28). As for HCC, there are limited studies that have investigated miR-638 and SOX2 expression and the clinical significance of this (29,30). Notably, whether or not an association exists between these two molecules remains to be elucidated.…”

Section: Expression Of Microrna 638 and Sex-determining Region Y-box mentioning

confidence: 99%

Expression of microRNA 638 and sex-determining region Y-box 2 in hepatocellular carcinoma: Association between clinicopathological features and prognosis

Guan

et al. 2018

Oncol Lett

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The aim of the present study was to determine the expression profile of microRNA 638 (miR-638) and sex-determining region Y-box 2 (SOX2) in hepatocellular carcinoma (HCC), and to investigate their association with clinicopathological features and survival. Reverse transcription-quantitative polymerase chain reaction analysis was used to investigate miR-638 and SOX2 expression in 78 patients with HCC. Western blot and immunohistochemical analyses were performed in order to determine SOX2 protein expression in HCC samples. Combined with the clinical postoperative follow-up data, the expression of miR-638 and SOX2 and the association between this and the prognostic values of patients with HCC were statistically analyzed. The results of the present study confirmed that miR-638 expression in tumor tissues was significantly downregulated (P<0.001), while SOX2 expression was significantly increased, compared with healthy control tissues (P<0.05). In addition, a significant inverse correlation between miR-638 and SOX2 expression was also observed in the HCC tissues (r=-0.675; P<0.05). Clinicopathological correlation analysis demonstrated that reduced miR-638 and elevated SOX2 expression was significantly associated with the Tumor-Node-Metastasis stage and portal vascular invasion (P<0.05). However, no significant differences were observed in other clinicopathological features, including age, sex, tumor size, tumor differentiation and hepatitis status (P>0.05). Notably, follow-up analysis revealed that patients with HCC with low miR-638 expression and high SOX2 expression tended to have a significantly shorter postoperative survival time (P<0.001). It was concluded that miR-638 may serve a vital role in the occurrence and progression of HCC by regulating SOX2 expression and thus, that miR-638 and SOX2 may be critical as novel diagnostic and prognostic biomarkers for HCC.

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Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by targeting SOX2 in hepatocellular carcinoma

Cited by 36 publications

References 30 publications

miR-488 acts as a tumor suppressor gene in gastric cancer

miR-488 acts as a tumor suppressor gene in gastric cancer

Methylation‑associated silencing of miR‑638 promotes endometrial carcinoma progression by targeting MEF2C

Expression of microRNA 638 and sex-determining region Y-box 2 in hepatocellular carcinoma: Association between clinicopathological features and prognosis

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