MicroRNA‑758 acts as a tumor inhibitor in colorectal cancer through targeting PAX6 and regulating PI3K/AKT pathway

Zhang, Xinli; Xu, Jumei; Zhang, Hongchang; Sun, Jilan; Li, Na; Huang, Xianyu

doi:10.3892/ol.2020.11516

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…miR‐758‐3p exhibited a tumor‐suppressive role in human cancers, including non‐small cell lung cancer, bladder cancer, cervical cancer, papillary thyroid cancer, colorectal cancer and breast cancer 14 15 , 27–30 Moreover, miR‐758‐3p could restrain cell proliferation and increase apoptosis in AML 16 . Similarly, we also validated the anti‐leukemogenic function of miR‐758‐3p, and found circ_0002483 could control AML progression by modulating miR‐758‐3p.…”

Section: Discussionmentioning

confidence: 54%

Hsa_circ_0002483 regulates miR‐758‐3p/MYC axis to promote acute myeloid leukemia progression

Xiao

2020

Hematological Oncology

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Circular RNAs are relevant to progression of acute myeloid leukemia (AML). Nevertheless, how and whether hsa_circ_0002483 (circ_0002483) participates in AML progression are largely uncertain. The bone marrow samples were harvested from 31 AML patients or 31 normal subjects. Circ_0002483, microRNA (miR)‐758‐3p and myelocytomatosis oncogene (MYC) abundances were examined via quantitative reverse transcription polymerase chain reaction and Western blot. Cell proliferation, cycle process and apoptosis were analyzed via Cell Counting Kit‐8, flow cytometry, caspase 3 activity and related protein levels. Target relationship was investigated by dual‐luciferase reporter assay and RNA immunoprecipitation. Circ_0002483 expression was elevated in AML patients and cells. Circ_0002483 silence constrained AML cell proliferation and facilitated cell cycle arrest and apoptosis. miR‐758‐3p was reduced in AML and decreased via circ_0002483. miR‐758‐3p down‐regulation mitigated the inhibitive influence of circ_0002483 interference on AML progression. MYC was decreased by miR‐758‐3p, and circ_0002483 could regulate MYC expression by miR‐758‐3p. miR‐758‐3p overexpression restrained cell proliferation and promoted cycle arrest and apoptosis via decreasing MYC. Circ_0002483 knockdown repressed AML cell proliferation and promoted cycle arrest and apoptosis via controlling miR‐758‐3p/MYC axis.

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Section: Discussionmentioning

confidence: 54%

Hsa_circ_0002483 regulates miR‐758‐3p/MYC axis to promote acute myeloid leukemia progression

Xiao

2020

Hematological Oncology

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“…PAX6 is also involved in a variety of key biological processes, including cell proliferation, migration, adhesion, signal transduction in normal development and tumorigenesis [ 29 , 30 ]. PAX6 showed the most interactions in the largest network, and has been reported to be a cancer driver in various cancers including lung [ 31–33 ] breast [ 30 ], colon [ 34 , 35 ], liver [ 36 ], pancreatic [ 36 ], and thyroid cancers [ 37 ]. Studies have shown that forced expression of PAX6 induces the formation of retinal heterotopic tissue [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNA ZFPM2-AS1 promotes retinoblastoma progression by targeting microRNA miR-511-3p/paired box protein 6 (PAX6) axis

2022

Bioengineered

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Long non-coding RNAs (lncRNAs) have been shown to play crucial roles in retinoblastoma progression. In this study, we aimed to investigate the mechanism of lncRNA ZFPM2-AS1 (ZFPM2-AS1) in retinoblastoma progression. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting assays were performed to determine the expression of lncRNA, microRNA (miRNA), mRNA, and protein. The changes in cell proliferation, apoptosis, and cell migration were assessed by functional experiments. The interaction between ZFPM2-AS1, miR-511-3p, and paired box protein 6 (PAX6) was confirmed by a luciferase assay. Our study found that ZFPM2-AS1 and PAX6 were upregulated, whereas miR-511-3p was downregulated in retinoblastoma. ZFPM2-AS1 inhibition decreased the viability and migration of retinoblastoma cells. We also found that ZFPM2-AS1 targets miR-511-3p to upregulate PAX6 in Y79 and SO-RB50 cells. Moreover, we demonstrated that inhibiting miR-511-3p reversed the negative effects of silencing ZFPM2-AS1 and PAX6 on retinoblastoma cell viability and migration. In conclusion, retinoblastoma development is regulated by the ZFPM2-AS1/511-3p/PAX6 axis.

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“…It is also possible that EG1 has an inhibitory effect on PAX6 as this protein has sequence homology with PAX2 and is expressed in HCT116 cells ( Figure 4 ). Furthermore, differing levels of PAX6 have been shown to regulate cell cycle progression in colorectal cancer cells with high levels leading to an increase in cell proliferation ( 31 ) through the modulation of PI3K/AKT signalling ( 32 ). It is therefore plausible that EG1 could also affect proliferation via PAX6.…”

Section: Discussionmentioning

confidence: 99%

Chemical Synthesis of the PAX Protein Inhibitor EG1 and Its Ability to Slow the Growth of Human Colorectal Carcinoma Cells

et al. 2021

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Colorectal cancer is primarily a disease of the developed world. The incidence rate has continued to increase over time, reflecting both demographic and lifestyle changes, which have resulted in genomic and epigenomic modifications. Many of the epigenetic modifications occur in genes known to be closely associated with embryonic development and cellular growth. In particular, the paired box (PAX) transcription factors are crucial for correct tissue development during embryogenesis due to their role in regulating genes involved in proliferation and cellular maintenance. In a number of cancers, including colorectal cancer, the PAX transcription factors are aberrantly expressed, driving proliferation and thus increased tumour growth. Here we have synthesized and used a small molecule PAX inhibitor, EG1, to inhibit PAX transcription factors in HCT116 colorectal cell cultures which resulted in reduced proliferation after three days of treatment. These results highlight PAX transcription factors as playing an important role in the proliferation of HCT116 colorectal cancer cells, suggesting there may be a potential therapeutic role for inhibition of PAX in limiting cancer cell growth.

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MicroRNA‑758 acts as a tumor inhibitor in colorectal cancer through targeting PAX6 and regulating PI3K/AKT pathway

Cited by 7 publications

References 31 publications

Hsa_circ_0002483 regulates miR‐758‐3p/MYC axis to promote acute myeloid leukemia progression

Hsa_circ_0002483 regulates miR‐758‐3p/MYC axis to promote acute myeloid leukemia progression

lncRNA ZFPM2-AS1 promotes retinoblastoma progression by targeting microRNA miR-511-3p/paired box protein 6 (PAX6) axis

Chemical Synthesis of the PAX Protein Inhibitor EG1 and Its Ability to Slow the Growth of Human Colorectal Carcinoma Cells

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