MiR-486-5p Targets CD133+ Lung Cancer Stem Cells through the p85/AKT Pathway

Moro, Massimo; Fortunato, Orazio; Bertolini, Giulia; Mensah, Mavis; Borzi, Cristina; Centonze, Giovanni; Andriani, Francesca; Paolo, Daniela Di; Perri, Patrizia; Ponzoni, Mirco; Pastorino, Ugo; Sozzi, Gabriella; Boeri, Mattia

doi:10.3390/ph15030297

Cited by 17 publications

(6 citation statements)

References 41 publications

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“…miR-486 is transcribed from the intron of the host gene ANK1 (Ankyrin 1) on human chromosome 8p11.21 [29]. There have been many reports describing miR-486-5p (the guide strand) in various cancer types [30][31][32][33]. Previous studies showed that the expression of miR-486-5p was reduced in cancer tissues, and that it functions as a tumor suppressor in breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, and renal cell carcinoma [34].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

Tomioka

Shioiri

Seki

et al. 2023

Cells

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The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downregulated in LUAD tissues. Ectopic expression of both miRNAs induced cell cycle arrest in LUAD cells, suggesting both strands of miRNAs derived from pre-miR-486 were tumor suppressive. Our in silico analysis showed a total of 99 genes may be under the control of both miRNAs in LUAD cells. Importantly, among these targets, the high expression of seven genes (MKI67, GINS4, RRM2, HELLS, MELK, TIMELESS, and SAPCD2) predicted a poorer prognosis of LUAD patients (p < 0.05). We focused on GINS4, a DNA replication complex GINS protein that plays an essential role in the initiation of DNA replication. Our functional assays showed that GINS4 was directly controlled by both strands of pre-miR-486, and its aberrant expression facilitated the aggressive behavior of LUAD cells. GINS4 is attractive as a therapeutic target for this disease. MiRNA analysis, including passenger strands, will further improve our understanding of the molecular pathogenesis of LUAD.

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Section: Discussionmentioning

confidence: 99%

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

Tomioka

Shioiri

Seki

et al. 2023

Cells

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“…Among non-coding RNA, miRNAs have been recognized as one of the major regulatory gene families during both normal development and carcinogenesis [ 34 ]. It has been demonstrated that miRNAs can act as both tumor suppressors [ 35 , 36 , 37 ], as well oncogenic miRNAs [ 36 , 38 , 39 ] in several types of cancers.…”

Section: Discussionmentioning

confidence: 99%

miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach

Santos

Portela

Camargo

et al. 2022

IJMS

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The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.

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“…On the other hand, miR-486-5p, a muscle-enriched miRNA found abundantly in plasma ( Bayés-Genis et al, 2018 ; Small et al, 2010 ) , demonstrates differential expression patterns across various cancers. It is downregulated in lung cancer ( Moro et al, 2022 ), steroid-induced osteonecrosis of the femoral head (SOFNH) ( Chen et al, 2023 ), papillary thyroid carcinoma ( Ma et al, 2016 ), breast cancer ( Li et al, 2019 ) and non-small cell lung cancer serum ( Xing et al, 2020 ), while being upregulated in cervical cancer ( Li et al, 2018 ) and sepsis patient serum ( Sun & Guo, 2021 ).…”

Section: Survey Methodologymentioning

confidence: 99%

The role of CEMIP in cancers and its transcriptional and post-transcriptional regulation

Guo,

Chen

et al. 2024

PeerJ

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CEMIP is a protein known for inducing cell migration and binding to hyaluronic acid. Functioning as a hyaluronidase, CEMIP primarily facilitates the breakdown of the extracellular matrix component, hyaluronic acid, thereby regulating various signaling pathways. Recent evidence has highlighted the significant role of CEMIP in different cancers, associating it with diverse pathological states. While identified as a biomarker for several diseases, CEMIP’s mechanism in cancer seems distinct. Accumulating data suggests that CEMIP expression is triggered by chemical modifications to itself and other influencing factors. Transcriptionally, chemical alterations to the CEMIP promoter and involvement of transcription factors such as AP-1, HIF, and NF-κB regulate CEMIP levels. Similarly, specific miRNAs have been found to post-transcriptionally regulate CEMIP. This review provides a comprehensive summary of CEMIP’s role in various cancers and explores how both transcriptional and post-transcriptional mechanisms control its expression.

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MiR-486-5p Targets CD133+ Lung Cancer Stem Cells through the p85/AKT Pathway

Cited by 17 publications

References 41 publications

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach

The role of CEMIP in cancers and its transcriptional and post-transcriptional regulation

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