Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis

Göhring, Axel R.; Reuter, Stefanie; Clement, Joachim H.; Cheng, Xinlai; Theobald, Jannick; Wölfl, Stefan; Mrowka, Ralf

doi:10.1371/journal.pone.0174912

Cited by 20 publications

(13 citation statements)

References 34 publications

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“…These results indicate that miRNA-299 and miRNA-7706 can inhibit tumor cell proliferation. This is consistent with the finding of Göhring et al ( 17 ) that miRNA-299 can inhibit the proliferation and invasion of tumor cells. Based on those studies, we speculate that miRNA-299 and miRNA-7706 can also regulate cell proliferation and invasion in HCC.…”

Section: Discussionsupporting

confidence: 93%

Prognostic value of hsa‑mir‑299 and hsa‑mir‑7706 in hepatocellular carcinoma

et al. 2018

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This study aimed to investigate the expression of microRNA (miRNA) 299 and miRNA-7706 in patients with hepatocellular carcinoma (HCC), and to explore their effects on proliferation of SK-HEP-1 HCC cells. Expression of miRNA-299 and miRNA-7706 in tumor tissue (HCC group) and adjacent healthy tissue (>30 mm away from the tumor tissue) of 179 patients with HCC was determined by real-time polymerase chain reaction (qRT-PCR). miR-299 mimics and miR-7706 mimics were transfected into SK-HEP-1 HCC cells by RNA transfection. The proliferation and invasion of SK-HEP-1 cells were detected by CCK-8 kit and Transwell kit, respectively. Compared with adjacent tissues, expression levels of miRNA-299 and miRNA-7706 in HCC group were significantly downregulated. Analyses on the correlation between the expression of miRNA-299 and miRNA-7706 and clinical factors showed that expression levels of miRNA-299 and miRNA-7706 were significantly correlated with pathological stages and lymph node metastasis. ROC curve analysis showed that the areas under the curve were 0.837 and 0.845 for miRNA-299 and miRNA-7706 in the prediction of HCC, respectively. Survival analysis showed that the 5-year overall survival rate of patients with high expression levels of miRNA-299 and miRNA-7706 was significantly different from that of patients with low expression levels (P=0.016). Compared with cells transfected with scramble mimics, proliferation and invasion abilities of SK-HEP-1 cells transfected with miR-299 mimics and miRNA-7706 were significantly weakened. Results suggested that downregulation of miRNA-299 and miRNA-7706 can inhibit the proliferation of HCC cells and can be used as a new target for the treatment of HCC.

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Section: Discussionsupporting

confidence: 93%

Prognostic value of hsa‑mir‑299 and hsa‑mir‑7706 in hepatocellular carcinoma

et al. 2018

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“…For example, miR-299-3p functioned as a tumor suppressor by inhibiting proliferation and invasion in human colon carcinoma (10). A similar inhibitory role of miR-299-3p was reported in breast cancer, where miR-299-3p suppressed the invasive behavior of cancer cells by targeting Oct4 (11). Additionally, Zheng et al (12) reported a role for miR-299-3p in the chemoresistance of lung cancer, as miR-299-3p promoted sensitivity to doxorubicin by directly targeting ATP-binding cassette E1.…”

Section: Introductionsupporting

confidence: 70%

Tumor‑suppressive miR‑299‑3p inhibits gastric cancer cell invasion by targeting heparanase

Zhou

2019

Mol Med Report

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Gastric cancer (Gc) remains a leading cause of cancer-associated mortality globally. emerging evidence suggests that micrornas (mirs) function as oncogenes or tumor suppressors, contributing to various aspects of cancer progression, including invasion and metastasis. in the present study, the specific role of miR-299-3p in the invasion of GC cells was investigated. The expression level of miR-299-3p was measured using reverse transcription-quantitative Pcr and in situ hybridization in human Gc tissues. effects of miR-299-3p on GC cell invasion were determined by Transwell assay. Bioinformatics and luciferase reporter assays were performed to identify and verify the downstream effectors of miR-299-3p. miR-299-3p expression analysis in clinical GC samples revealed a significant downregulation of miR-299-3p compared with non-tumor tissues. Inhibition of miR-299-3p promoted the invasive abilities of Gc cells, whereas its overexpression significantly suppressed cell invasion. Bioinformatics and luciferase reporter assays identified heparanase (HPSE) as a direct target of miR-299-3p, the ectopic expression of which reversed the impairment in cell invasion induced by miR-299-3p upregulation. Furthermore, HPSE expression was negatively associated with miR-299-3p levels in human GC tissues. Overall, the present study indicated that miR-299-3p functions as a tumor suppressor by directly targeting HPSE, highlighting its potential as a target for the treatment of Gc.

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“…Aberrant regulation of miRNAs is involved in controlling stemness in multiple cancers by modulating stemness-related genes [39][40][41]. MiR-34a is a tumor suppressor miRNA and is downregulated in many malignancies, for example, human liver cancer [10,11].…”

Section: Discussionmentioning

confidence: 99%

The DNMT1/miR-34a/FOXM1 Axis Contributes to Stemness of Liver Cancer Cells

Cao

Liu

Cao

et al. 2020

Journal of Oncology

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Background. Whether DNA methyltransferase 1 (DNMT1)/miR-34a/FoxM1 signaling promotes the stemness of liver cancer stem cells (LCSCs) remains unclear. This study aimed to assess whether methylation-based silencing of miR-34a by DNMT1 contributes to stemness features via FoxM1 upregulation in LCSCs. Methods. The CD133+ subgroup of MHCC97H cells sorted by MACS was used as LCSCs. DNMT1, BMI1, SOX2, and OCT4 mRNA levels, and miR-34a amounts were determined by qRT-PCR. DNMT1, CD44, and FoxM1 proteins were analyzed by immunoblot. Sphere and colony formation abilities were detected by respective assays. CD133+ cell percentages were assessed by flow cytometry. In vivo oncogenicity was evaluated using a tumor xenograft model in mice. The effects of DNMT1/miR-34a signaling on the stemness of LCSCs were examined by knockdown or overexpression of DNMT1 and/or transfection of miR-34a mimic or inhibitor using lentivirus-delivery systems. FoxM1 association with miR-34a was detected by a reporter assay. Results. We here showed that LCSCs exhibited elevated DNMT1 activity and expression, lower miR-34a expression with higher promoter methylation, and stronger stemness, compared with the parental liver cancer cells. DNMT1 knockdown repressed DNMT1, increased miR-34a amounts by promoter demethylation, and reduced stemness in LCSCs, whereas DNMT1 overexpression had the opposite effects in liver cancer cells. Transfection with miR-34a mimic repressed the stemness of LCSCs, while miR-34a inhibitor significantly downregulated miR-34a and enhanced stemness, without affecting DNMT1 in liver cancer cells. MiR-34a mimic rescued the effects of DNMT1 overexpression on the stemness of LCSCs, without affecting DNMT1 expression. Finally, FOXM1 was identified as a direct target by miR-34a in LCSCs. Conclusions. We revealed that aberrant activation of DNMT1 causes miR-34a promoter methylation and suppression, leading to FoxM1 upregulation by disinhibition and promotion of LCSC stemness. These findings suggest that blockage of DNMT1/miR-34a-mediated FOXM1 upregulation might suppress liver cancer by targeting LCSCs.

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Human microRNA-299-3p decreases invasive behavior of cancer cells by downregulation of Oct4 expression and causes apoptosis

Cited by 20 publications

References 34 publications

Prognostic value of hsa‑mir‑299 and hsa‑mir‑7706 in hepatocellular carcinoma

Prognostic value of hsa‑mir‑299 and hsa‑mir‑7706 in hepatocellular carcinoma

Tumor‑suppressive miR‑299‑3p inhibits gastric cancer cell invasion by targeting heparanase

The DNMT1/miR-34a/FOXM1 Axis Contributes to Stemness of Liver Cancer Cells

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