27P MiR-939-5p exhibits tumour suppressor activity and immune surveillance manipulation in triple-negative breast cancer

Nafea, Heba; Youness, R.A.; Abou-Aisha, Khaled

doi:10.1016/j.annonc.2021.01.041

Cited by 3 publications

(2 citation statements)

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“…miR-939-5p is expressed aberrantly in a diverse range of malignancies and works to inhibit cancer progression. [29][30][31] Both linc02231 and miR-939-5p bind to AGO2 protein, which has shearing activity and is involved in the assembly process of miRNAs and is a core component of the RISC that mediates mRNA degradation, instability, and transcriptional repression. 32,33 The hnRNPA1 is a well-known splicing factor.…”

Section: Discussionmentioning

confidence: 99%

STAT2‐induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer

Fang

Chang

et al. 2023

The Journal of Gene Medicine

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Background Long non‐coding RNAs (lncRNAs) play a critical role in regulating various human diseases including cancer. In colorectal cancer (CRC), there are still some undervalued lncRNAs with potential functions and mechanisms that need to be clarified. The present study aimed to investigate the role of linc02231 in the progression of CRC. Methods The proliferation of CRC cells was evaluated using Cell Counting Kit‐8, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays. Cell migration was examined through wound healing and Transwell analyses. The impact of linc02231 on angiogenesis was determined through a tube formation assay. Western blotting was used to detect the expression of specific proteins. A mouse xenograft model is established to observe the effect of linc02231 on the in vivo growth of CRC cells. Target genes of linc02231 are screened using high‐throughput sequencing. The transcriptional activity of STAT2 on linc02231 and the binding activity between linc02231/miR‐939‐5p/hnRNPA1 were analyzed by a luciferase assay. Results Based on public databases and comprehensive bioinformatics analysis, we found that lncRNA linc02231 was upregulated in CRC tumor tissues, which is consistent with our clinical results. linc02231 promoted the proliferation and migration of CRC cells in vitro and their tumorigenicity in vivo. Furthermore, linc02231 promotes the angiogenic ability of human umbilical vein endothelial cells. Mechanistically, the transcription factor STAT2 binds to the promoter region of linc02231 and activates its transcription. linc02231 also competes with miR‐939‐5p for binding to the pro‐oncogenic target gene hnRNPA1, preventing its degradation. hnRNPA1 prevents the maturation of angiopoietin‐like protein 4 (ANGPTL4) messenger RNA, leading to impaired tumor angiogenesis and increased metastasis of CRC. Conclusions The expression of linc02231, which is induced by STAT2, has been found to enhance the proliferation, metastasis, and angiogenesis of CRC by binding to miR‐939‐5p and increasing the expression of hnNRPA1 at the same time as suppressing ANGPTL4. These findings suggest that linc02231 could serve as a potential biomarker and therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 99%

STAT2‐induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer

Fang

Chang

et al. 2023

The Journal of Gene Medicine

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“…Thus, the pharmacological inhibitors of H 2 S-synthesizing enzymes did not show consistent outcomes, due to selectivity and dose- and time-adjustment issues [ 85 ]. Accordingly, molecular genetics therapeutic tools such as microRNAs (miRNAs), short hairpin RNAs (shRNAs), and small interfering RNAs (siRNAs) provide promising approaches that would allow for the specific targeting of H 2 S-synthesizing enzymes [ 79 , 84 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ]. The following part of the review focuses on the possible mechanisms through which such RNA-based molecular genetics targeting approaches could be used and delivered to brain tumors.…”

Section: Modern Rna-based Therapeutic Modalitiesmentioning

confidence: 99%

Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

Fahmy¹,

Dawoud

Zeinelabdeen

et al. 2022

Cancers

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Pediatric brain tumors represent a formidable challenge in the field of oncology. Pediatric brain tumors are sub-classified into several molecular sub-types, where each one is characterized by an array of hyperactivated oncogenic molecular engines. However, there have been great efforts dedicated to portray the involved signaling pathways driving pediatric brain tumors. Yet, a full understanding of the intertwined oncogenic pathways involved is still obscure. In this review, the authors shed light on novel therapeutic targets tailored for several sub-types of pediatric brain tumors and point out the limitations of such therapeutic approaches. Hydrogen Sulfide (H2S) has recently been cast as an oncogenic driver in several solid malignancies, yet its role in brain tumors is still under investigation. The authors also highlight the possible involvement of H2S in pediatric brain tumors and propose promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumors patients.Abstract: Pediatric primary brain tumors represent a real challenge in the oncology arena. Besides the psychosocial burden, brain tumors are considered one of the most difficult-to-treat malignancies due to their sophisticated cellular and molecular pathophysiology. Notwithstanding the advances in research and the substantial efforts to develop a suitable therapy, a full understanding of the molecular pathways involved in primary brain tumors is still demanded. On the other hand, the physiological nature of the blood–brain barrier (BBB) limits the efficiency of many available treatments, including molecular therapeutic approaches. Hydrogen Sulfide (H2S), as a member of the gasotransmitters family, and its synthesizing machinery have represented promising molecular targets for plentiful cancer types. However, its role in primary brain tumors, generally, and pediatric types, particularly, is barely investigated. In this review, the authors shed the light on the novel role of hydrogen sulfide (H2S) as a prominent player in pediatric brain tumor pathophysiology and its potential as a therapeutic avenue for brain tumors. In addition, the review also focuses on the challenges and opportunities of several molecular targeting approaches and proposes promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumor patients.

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The functional significance and cross-talk of non-coding RNAs in triple negative and quadruple negative breast cancer

Paul

Banerjee

2022

Mol Biol Rep

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27P MiR-939-5p exhibits tumour suppressor activity and immune surveillance manipulation in triple-negative breast cancer

Cited by 3 publications

References 0 publications

STAT2‐induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer

STAT2‐induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer

Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

The functional significance and cross-talk of non-coding RNAs in triple negative and quadruple negative breast cancer

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