miRNA-mRNA Regulatory Network Reveals miRNAs in HCT116 in Response to Folic Acid Deficiency via Regulating Vital Genes of Endoplasmic Reticulum Stress Pathway

Lü, Lin; Zhao, Hang; Li, Jianjun; Zhang, Kun; Wang, Xu

doi:10.1155/2021/6650181

Cited by 5 publications

(3 citation statements)

References 56 publications

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“…The most important interactions in C6 were HSP90B1-CALR (RIA = 0.50), HSPA5-HSP90B1 (RIA = 0.42) and HSPA5-CALR (RIA = 0.39). All three of this genes are regulated by ATF6 (see REACTOME, also ( 43 )). In Ciliated cells, several genes also showed frequent interactions with RSPH1 such as RSPH1-RUVBL1 (RIA = 0.22) and RSPH1- IGFBP7 (RIA = 0.18).…”

Section: Resultsmentioning

confidence: 99%

Single-cell gene regulatory network prediction by explainable AI

Keyl

Bischoff

Dernbach

et al. 2023

Nucleic Acids Research

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The molecular heterogeneity of cancer cells contributes to the often partial response to targeted therapies and relapse of disease due to the escape of resistant cell populations. While single-cell sequencing has started to improve our understanding of this heterogeneity, it offers a mostly descriptive view on cellular types and states. To obtain more functional insights, we propose scGeneRAI, an explainable deep learning approach that uses layer-wise relevance propagation (LRP) to infer gene regulatory networks from static single-cell RNA sequencing data for individual cells. We benchmark our method with synthetic data and apply it to single-cell RNA sequencing data of a cohort of human lung cancers. From the predicted single-cell networks our approach reveals characteristic network patterns for tumor cells and normal epithelial cells and identifies subnetworks that are observed only in (subgroups of) tumor cells of certain patients. While current state-of-the-art methods are limited by their ability to only predict average networks for cell populations, our approach facilitates the reconstruction of networks down to the level of single cells which can be utilized to characterize the heterogeneity of gene regulation within and across tumors.

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Section: Resultsmentioning

confidence: 99%

Single-cell gene regulatory network prediction by explainable AI

Keyl

Bischoff

Dernbach

et al. 2023

Nucleic Acids Research

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“…It has been demonstrated that the upregulation of miR-23a-3p suppressed oxidative stress in ischemic brain injury using a mouse model [ 27 ]. Moreover, it has been shown that folic acid deficiency might upregulate miR-30d-5p to inhibit the expression of key genes in the endoplasmic reticulum stress pathway in colorectal cancer cells [ 28 ]. This suggests the possible involvement of miR-30d-5p in the cellular response to folic acid deficiency in SB pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance

Buczyńska,

Sidorkiewicz,

Niemira

et al. 2024

IJMS

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Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB.

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“…MicroRNAs are a type of short noncoding RNAs (~22 nucleotides) important in regulating cellular response and function, including UPR [69,70]. Several miRNAs such as miR-30d [71,72], miR-199a-3p or miR-199a-5p [73], miR-214 [73], miR-379-5p [71,72], and miR-7112-3p [74] were reported to target Grp78, thus affecting protein folding and leading to ERS. The understanding of the involvement and role of miRNA in tocotrienolmediated ERS is very limited.…”

Section: Novel Approaches In Studying Tocotrienol-mediated Ersmentioning

confidence: 99%

Molecular Mechanism of Tocotrienol-Mediated Anticancer Properties: A Systematic Review of the Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response

Pang

Chin

2023

Nutrients

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Background: Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol. Method: A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered. Result: A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown. Conclusion: ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.

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miRNA-mRNA Regulatory Network Reveals miRNAs in HCT116 in Response to Folic Acid Deficiency via Regulating Vital Genes of Endoplasmic Reticulum Stress Pathway

Cited by 5 publications

References 56 publications

Single-cell gene regulatory network prediction by explainable AI

Single-cell gene regulatory network prediction by explainable AI

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance

Molecular Mechanism of Tocotrienol-Mediated Anticancer Properties: A Systematic Review of the Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response

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