Transcriptional activation of the IGF-II/IGF-1R axis and inhibition of IGFBP-3 by miR-155 in hepatocellular carcinoma

Tayebi, H.M. El; Waly, Amr A.; Assal, R.A.; Hosny, Karim Adel; Esmat, Gamal; Abdelaziz, Ahmed Ihab

doi:10.3892/ol.2015.3725

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…Then, dual-luciferase reporter assay also determined that IGFBP3 was a target mRNA of miR-409-3p in OS. Interestingly, previous studies determined that IGFBP3 was a target mRNA of miR-196b, miR-1290, miR-384, miR-34/449 and miR-155 in cancers [ 37 – 40 ], but the regulatory mechanism of miR-409-3p/IGFBP3 has not been verified in OS. Accumulating researches indicated that IGFBP3 played an important role in regulating cell cycle and apoptosis in various cancers, including breast cancer, nasopharyngeal carcinoma, OS, etcetera [ 41 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis

Long

Gong

et al. 2020

Cancer Cell Int

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Background Circular RNAs (circRNAs) are important regulators in the pathogenesis of diseases and affects the occurrence and development of diseases. However, the role of circRNAs in osteosarcoma (OS) has not been fully elucidated. Methods The expression of circ_0000285, miR-409-3p and insulin-like growth factor binding protein 3 (IGFBP3) was detected using quantitative real-time PCR (qRT-PCR). The protein level of IGFBP3 was measured using western blot. CCK-8 and colony formation assays were used to determine cell proliferation. Flow cytometry was applied to measure cell cycle and cell apoptosis. Transwell assay was used to assess cell invasion and migration. Dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) assay were performed to determine the relationship among circ_0000285, miR-409-3p and IGFBP3. The animal experiments were performed to determine the function of circ_0000285 in vivo. Results In this study, we found that the expression of circ_0000285 was significantly increased in OS tissues and cells and was enriched in the cytoplasm. Knockdown of circ_0000285 inhibited OS growth in vitro and in vivo. Moreover, miR-409-3p was a target miRNA of circ_0000285 and miR-409-3p targets to IGFBP3 in OS. Besides, circ_0000285 could promote proliferation, migration, invasion and inhibit apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis. Conclusion In this study, circ_0000285 regulated proliferation, migration, invasion and apoptosis of OS cells by miR-409-3p/IGFBP3 axis, implying that circ_0000285 was a potential target for OS therapy.

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Section: Discussionmentioning

confidence: 99%

Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis

Long

Gong

et al. 2020

Cancer Cell Int

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“…Other than methylation and proteolysis, miRNA regulation may be another mode for IGFBP3 inactivation. For example, miR-21 enhances glioblastoma tumorigenesis by downregulating IGFBP3 (29); onco-miRs miR-155 and miR-125b also target IGFBP3, promoting migration and invasion in HCC and NSCLC through the IGF-II/IGF-1R axis (30) and downstream PI3K/AKT activation (31). miRNAs regulate complementary mRNAs by inducing translational suppression and mRNA destablization.…”

Section: Discussionmentioning

confidence: 99%

miR‑197 promotes the invasion and migration of colorectal cancer by targeting insulin‑like growth factor‑binding protein�3

Zhou

Sun

et al. 2018

Oncol Rep

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The incidence and mortality of colorectal cancer (CRC) have been rising rapidly in China. A number of miRNAs have been confirmed to be involved in diverse biological processes of CRC. However, whether miR‑197 plays a role in migration and invasion of CRC has never been explored. In the present study Transwell chambers were used in in vitro migration and invasion assays. Dual-luciferase reporter assay was employed to confirm the target of miR‑197. RT‑PCR and IHC staining were performed to quantify miR‑197 and IGFBP3 expression, respectively. Clinicopathological features were collected for statistical analysis. We observed that the overexpression of miR‑197 significantly promoted migration and invasion in 3 CRC cell lines including HCT8, HCT116 and SW480 (P<0.05), while the inhibition of miR‑197 weakened both biological processes (P<0.05). In bioinformatics and dual-luciferase reporter assay, luciferase activities of IGFBP3‑WT‑transfected cells significantly decreased upon miR‑197 overexpression and this inhibitory effect was abolished when miR‑197 binding region in IGFBP3 3'‑UTR was mutated, which indicated that miR‑197 directly suppressed the expression of IGFBP3 in CRC cells by targeting its 3'UTR. Downregulation of the expression of IGFBP3 by using targeted siRNA led to significant enhancement of cell migration and invasion in two CRC cell lines including HCT8 and HCT116 (P<0.05). Finally, in cancerous tissues of CRC patients, the miR‑197 level was inversely correlated with the expression of IGFBP3 (P=0.026), which indicated that miR‑197 may modulate cell migration and invasion by targeting IGFBP3 in CRC patients. In conclusion, we revealed that miR‑197 modulates IGFBP3 and therefore plays a critical role in regulating CRC migration and invasion.

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“…In order to understand the molecular mechanisms by which miR-let-7a performs its tumor-suppressive function in HCC, we intended to define networks of miR-let-7a targets, which might be involved in the regulation of tumor-relevant pathways. Since we are mainly interested in the IGF signaling pathway and its role in hepatocarcinogenesis (El Tayebi et al, 2011, 2015; Assal et al, 2015; Fawzy et al, 2016; Habashy et al, 2016; Youness et al, 2016; Rahmoon et al, 2017), we selected IGF-axis members potentially targeted by miR-let-7a using in silico microRNA target prediction softwares. This analysis yielded IGFII, IGF2BP2 as well as IGF2BP3 as potential miR-let-7a targets (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Methylation in MIRLET7A3 Gene Induces the Expression of IGF-II and Its mRNA Binding Proteins IGF2BP-2 and 3 in Hepatocellular Carcinoma

Waly

El-Ekiaby²,

Assal

et al. 2019

Front. Physiol.

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miR-let-7a is a tumor suppressor miRNA with reduced expression in most cancers. Methylation of MIRLET7A3 gene was reported to be the cause of this suppression in several cancers; however, it was not explicitly investigated in hepatocellular carcinoma (HCC). We aimed at investigating miR-let-7a expression and molecular mode in HCC, identifying drug-targetable networks, which might be affected by its abundance. Our results illustrated a significant repression of miR-let-7a, which correlated with hypermethylation of its gene of origin MIRLRT7A3. This was further supported by the induction of miR-let-7a expression upon treatment of HCC cells with a DNA-methyltransferase inhibitor. Using a computational approach, insulin-like growth factor (IGF)-II and IGF-2 mRNA binding proteins (IGF2BP)-2/-3 were identified as potential targets for miR-let-7a that was further confirmed experimentally. Indeed, miR-let-7a mimics diminished IGF-II as well as IGF2BP-2/-3 expression. Direct binding of miR-let-7a to each respective transcript was confirmed using a luciferase reporter assay. In conclusion, this study suggests that DNA hypermethylation leads to epigenetic repression of miR-let-7a in HCC cells, which induces the oncogenic IGF-signaling pathway.

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Transcriptional activation of the IGF-II/IGF-1R axis and inhibition of IGFBP-3 by miR-155 in hepatocellular carcinoma

Cited by 23 publications

References 41 publications

Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis

Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis

miR‑197 promotes the invasion and migration of colorectal cancer by targeting insulin‑like growth factor‑binding protein�3

Methylation in MIRLET7A3 Gene Induces the Expression of IGF-II and Its mRNA Binding Proteins IGF2BP-2 and 3 in Hepatocellular Carcinoma

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