MicroRNA-34 Family in Cancers: Role, Mechanism, and Therapeutic Potential

Fu, Junjiang; Imani, Saber; Wu, Mei-Yi; Wu, Ray-Chang

doi:10.3390/cancers15194723

Cited by 11 publications

(6 citation statements)

References 186 publications

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“…Similar to circRNAs, miRNAs belong to the non-coding RNA family. In contrast to circRNAs, miRNAs specifically bind to the 3′-UTR region of downstream target mRNAs, thereby facilitating mRNA degradation or suppressing their protein translation (Fu et al 2023 ). In this research, NEDD4L was identified as a downstream target gene regulated by miR-665.…”

Section: Discussionmentioning

confidence: 99%

circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis

Wu,

Wang,

Zhang

et al. 2024

Cell Biol Toxicol

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Air pollution has greatly increased the risk of idiopathic pulmonary fibrosis (IPF). Circular RNAs (circRNAs) have been found to play a significant role in the advancement of IPF, but there is limited evidence of correlation between circRNAs and lung epithelial cells (LECs) in IPF. This research aimed to explore the influence of circRNAs on the regulation of EMT progression in LECs, with the objective of elucidating its mechanism and establishing its association with IPF. Our results suggested that the downregulation of circGRHPR in peripheral blood of clinical cases was associated with the diagnosis of IPF. Meanwhile, we found that circGRHPR was downregulated in transforming growth factor-beta1 (TGF-β1)–induced A549 and Beas-2b cells. It is a valid model to study the abnormal EMT progression of IPF-associated LECs in vitro. The overexpression of circGRHPR inhibited the abnormal EMT progression of TGF-β1-induced LECs. Furthermore, as the sponge of miR-665, circGRHPR released the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), thus promoting its downstream transforming growth factor beta receptor 2 (TGFBR2) ubiquitination. It is helpful to reduce the response of LECs to TGF-β1 signaling. In summary, circGRHPR/miR-665/NEDD4L axis inhibited the abnormal EMT progression of TGF-β1-induced LECs by promoting TGFBR2 ubiquitination, which provides new ideas and potential targets for the treatment of IPF. Graphical Abstract Graphical headlights 1. Downregulation of circGRHPR in peripheral blood is associated with clinical diagnosis of IPF. 2. circGRHPR inhibits the abnormal EMT progression of TGF-β1-induced LECs in vitro. 3. circGRHPR/miR-665/NEDD4L axis inhibits the abnormal EMT progression of TGF-β1-induced LECs by promoting ubiquitination of TGFBR2 in vitro.

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Section: Discussionmentioning

confidence: 99%

circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis

Wu,

Wang,

Zhang

et al. 2024

Cell Biol Toxicol

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“…miR-34a acts differently in colorectal cancer compared to its role in prostate cancer, according to its interaction with tissue-specific cofactors and targets [ 193 ].…”

Section: Tissue-specific Roles Of Mirnas In Cancermentioning

confidence: 99%

“…miR-34a, directly transactivated by p53, influences tumor cells and impacts immune cells by modulating cytokine profiles and T-cell activation, critical for immune surveillance and antitumor immunity [ 193 , 199 ].…”

Section: Role Of Mirnas In Modulating Immune Cell Dynamics In the Can...mentioning

confidence: 99%

How MicroRNAs Command the Battle against Cancer

Wu,

Leng,

Sergi

et al. 2024

IJMS

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MicroRNAs (miRNAs) are small RNA molecules that regulate more than 30% of genes in humans. Recent studies have revealed that miRNAs play a crucial role in tumorigenesis. Large sets of miRNAs in human tumors are under-expressed compared to normal tissues. Furthermore, experiments have shown that interference with miRNA processing enhances tumorigenesis. Multiple studies have documented the causal role of miRNAs in cancer, and miRNA-based anticancer therapies are currently being developed. This review primarily focuses on two key points: (1) miRNAs and their role in human cancer and (2) the regulation of tumor suppressors by miRNAs. The review discusses (a) the regulation of the tumor suppressor p53 by miRNA, (b) the critical role of the miR-144/451 cluster in regulating the Itch-p63-Ago2 pathway, and (c) the regulation of PTEN by miRNAs. Future research and the perspectives of miRNA in cancer are also discussed. Understanding these pathways will open avenues for therapeutic interventions targeting miRNA regulation.

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“…Research is still ongoing to improve the accessibility of miR-34 family members in translational research and clinical practice in respect to the treatment of breast cancer [41], colon cancer [42], lung cancer [43], oral cancer [44], oesophageal cancer [45] and some others (reviewed in [46]).…”

Section: Functions Of Small Non-coding Rnas and Their Modulation By E...mentioning

confidence: 99%

Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family

Štefánik,

Morová,

Herichová

2024

Biomedicines

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The present review focuses on the interactions of newly emerging environmental factors with miRNA-mediated regulation. In particular, we draw attention to the effects of phthalates, electromagnetic fields (EMFs) and a disrupted light/dark cycle. miRNAs are small non-coding RNA molecules with a tremendous regulatory impact, which is usually executed via gene expression inhibition. To address the capacity of environmental factors to influence miRNA-mediated regulation, the miR-34 family was selected for its well-described oncostatic and neuro-modulatory properties. The expression of miR-34 is in a tissue-dependent manner to some extent under the control of the circadian system. There is experimental evidence implicating that phthalates, EMFs and the circadian system interact with the miR-34 family, in both lines of its physiological functioning. The inhibition of miR-34 expression in response to phthalates, EMFs and light contamination has been described in cancer tissue and cell lines and was associated with a decline in oncostatic miR-34a signalling (decrease in p21 expression) and a promotion of tumorigenesis (increases in Noth1, cyclin D1 and cry1 expressions). The effects of miR-34 on neural functions have also been influenced by phthalates, EMFs and a disrupted light/dark cycle. Environmental factors shifted the effects of miR-34 from beneficial to the promotion of neurodegeneration and decreased cognition. Moreover, the apoptogenic capacity of miR-34 induced via phthalate administration in the testes has been shown to negatively influence germ cell proliferation. To conclude, as the oncostatic and positive neuromodulatory functions of the miR-34 family can be strongly influenced by environmental factors, their interactions should be taken into consideration in translational medicine.

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MicroRNA-34 Family in Cancers: Role, Mechanism, and Therapeutic Potential

Cited by 11 publications

References 186 publications

circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis

circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis

How MicroRNAs Command the Battle against Cancer

Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family

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