microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma

Yu, Zhaoxiang; Lin, Xiaolan; Tian, Ming; Chang, Weiping

doi:10.3892/or.2017.6130

Cited by 18 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, miR-196a was reported to contribute to cell proliferation through regulating cell cycle via targeting FOXO1 in HCC 23 . As for miR-196b, it was shown to predict poor prognosis and increase cell migration as well as invasion in HCC by regulating FOXP2 24 . Consistently with these reports, we also found that miR-196a and miR-196b knockdown could induce proliferation and apoptosis inhibition and indicate poor outcome of patients.…”

Section: Discussionmentioning

confidence: 99%

“…Functional miRNAs are known to regulate targets expressions by binding their 3′-UTR sequences 26 . This research explored multiple targets of miR-196a and miR-196b and previous studies have validated the interaction between them and FOXO1, FOXP2, or lysosomeassociated protein transmembrane-4β (LAPTM4B) in HCC [22][23][24]27 . SOCS proteins mediate inflammation and apoptosis via regulating immune homeostasis in human cancers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

Ren

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

microRNAs (miRNAs) play essential roles in progression of hepatocellular carcinoma (HCC). However, the roles of miR-196a and miR-196b as well as mechanism in HCC progression remain poorly understood. The expressions of miR-196a, miR-196b and suppressor of cytokine signaling 2 (SOCS2) were measured in HCC tissues and cells by quantitative realtime polymerase chain reaction or immunohistochemistry. HCC progression was investigated by cell proliferation, glycolysis, cycle, clones, apoptosis, and necrosis. The interaction between SOCS2 and miR-196a or miR-196b was explored by luciferase activity and RNA immunoprecipitation analyses. The expressions of proteins in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway were measured by western blot. A xenograft model was established to investigate the roles of miR-196a or miR-196b in vivo. We found that miR-196a and miR-196b were highly expressed in HCC tissues and cells. High expression of miR-196a or miR-196b was correlated with tumor size, tumor-node-metastasis stage, lymph node metastasis, albumin-bilirubin grade and poor 5-year survival. Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in HCC cells. SOCS2 was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. SOCS2 was negatively associated with activation of the JAK/STAT pathway. Besides, knockdown of miR-196a or miR-196b limited xenograft tumor growth by blocking the JAK/STAT pathway. We concluded that downregulation of miR-196a or miR-196b inhibited HCC progression through regulating the JAK/STAT pathway via targeting SOCS2, providing novel targets for prognosis and therapeutics of HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

Ren

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Numerous miRNAs are downregulated or upregulated in HCC, such as miR-21 (13), miR-493 (14), miR-873 (15) and miR-3662 (16). Upregulated miRNAs usually serve as oncogenes (17,18), whereas lowly expressed miRNAs display tumor-suppressor activity (19,20) in regards to HCC initiation and development. Therefore, inhibition or restoration of a specific miRNA might be an effective therapeutic technique for HCC treatment.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin

et al. 2018

View full text Add to dashboard Cite

Numerous microRNAs (miRNAs) have been demonstrated to be downregulated or upregulated in hepatocellular carcinoma (HCC) and play important roles in its occurrence and development. Therefore, the investigation of miRNAs and their functions implicated in the genesis and development of HCC may provide key clues for the identification of effective therapeutic approaches for patients with this disease. The aims of the present study were to detect miRNA-466 (miR-466) expression in HCC tissues and cell lines and to determine its effects on HCC cell proliferation, apoptosis and metastasis, as well as to explore the mechanisms underlying the tumor-suppressing roles of miR-466 in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-466 expression in HCC tissues and cell lines. The effects of miR-466 upregulation on HCC cell proliferation, apoptosis, migration and invasion were determined using Cell Counting Kit-8 assay, flow cytometry analysis and Transwell chamber assay, respectively. The potential target gene of miR-466 was predicted using bioinformatic analysis, which was further confirmed by luciferase reporter assay, RT-qPCR and western blot analysis. It was found that miR-466 was obviously decreased in HCC tissues and cell lines. The results of functional experiments revealed that restoration of miR-466 expression suppressed the proliferation, induced apoptosis, and reduced the metastasis of HCC cells. In addition, metadherin (MTDH) was identified as a direct target of miR-466 in HCC cells. Furthermore, MTDH was upregulated in HCC tissues, which was inversely correlated with the miR-466 level. Moreover, inhibition of MTDH displayed similar tumor-suppressing roles as miR-466 upregulation in HCC cells. In addition, MTDH reintroduction restored the tumor-suppressor activity of miR-466 overexpression in HCC cells. These findings suggest that miR-466 is a potential therapeutic tool for HCC therapy.

show abstract

“…Interestingly, these authors also con rmed these results in vivo in a nude mouse model [17]. Furthermore, it should be noted that FOXP2 has also been associated with the promotion of migration and invasion of tumor cellsin breast cancer [26,27], hepatocellular carcinoma [14], prostate cancer [10] and colorectal carcinoma [28], among others. Therefore, results from in vitro studies suggest that FOXP2 may promote the malignant biological behavior of glioma cells.…”

Section: Foxp2 Expression In Glioblastomamentioning

confidence: 68%

“…On the one hand, high expression of FOXP2 has been associated with a bad prognosis in prostate cancer [10], neuroblastoma [11] and multiple mieloma [12]. On the other hand, other studies have reported an association between FOXP2 expression and a better prognosis in breast cancer [13], liver cell carcinoma [14], osteosarcoma [15] and gastric cancer [16]. Thus, whether FOXP2 is a tumor suppressor or tumor-promoting gene is matter of controversy.…”

Section: Introductionmentioning

confidence: 99%

Low Expression of FOXP2 is Associated with Better Prognosis in Glioblastoma.

Plata‐Bello

Fariña-Jerónimo

Betancor

2020

Preprint

View full text Add to dashboard Cite

FOXP2 expression has been associated with the prognosis of some tumors, but the role of FOXP2 in glioblastoma has not been studied in-depth until now. The aim of the present work is to study the role of FOXP2 as a prognostic biomarker in glioblastoma.This is a retrospective observational case series study in which the expression of FOXP2 has been analyzed both at the protein level (immunohistochemistry) and at the mRNA level (RNAseq, in a cohort of glioblastoma patients from The Cancer Genome Atlas [TCGA] database). Other molecular and clinical data have also been included in the study, with special focus on miRNA expression data.Survival analysis using Log-Rank test and COX-regression have been used. Non-parametric statistical tests were also used to study differences between low and high FOXP2 expression groups.Patients with a high expression of FOXP2 protein showed a worse prognosis than those patients with low expression in both, progression free survival (PFS) (HR=1.711; p=0.034) and overall survival (OS) (HR=1.809;p=0.014). These associations were still statistically significant in multivariate analysis.No prognostic association was found with FOXP2 RNA expression. Interestingly, two miRNAs that target FOXP2 (hsa-miR-181a-2-3p and hsa-miR-20a-3p) showed an interaction effect on OS with FOXP2 expression. A low level of these miRNAs expression was associated with a significantly worse prognosis in patients with high FOXP2 RNA expression.Higher expression of FOXP2 at the protein level is associated with a worse prognosis. This protein expression may be regulated by the expression of specific miRNAs that target FOXP2 mRNA: hsa-miR-181a-2-3p and hsa-miR-20a-3p.

show abstract

microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma

Cited by 18 publications

References 27 publications

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

MicroRNA‑466 inhibits the aggressive behaviors of hepatocellular carcinoma by directly targeting metadherin

Low Expression of FOXP2 is Associated with Better Prognosis in Glioblastoma.

Contact Info

Product

Resources

About