YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

Li, Jie; Wu, Lei; Pei, Meili; Zhang, Yun

doi:10.1186/s13048-020-00717-5

Cited by 62 publications

(59 citation statements)

References 27 publications

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“…Acridine Orange assays show that high levels of miR-145 increase apoptosis of zebrafish embryonic cells, suggesting that NCCs may die before differentiation ( Figure 6 ). This finding agrees with data gathered in embryonic and cancer cultured cell lines, wherein miR-145 overexpression promotes apoptosis and reduces cell viability [ 16 , 34 , 69 , 77 , 78 ]. These observations as a whole could suggest that miR-145 participates in the control of cell death regulation in both normal and pathological conditions.…”

Section: Discussionsupporting

confidence: 92%

Conservation of Zebrafish MicroRNA-145 and Its Role during Neural Crest Cell Development

Steeman

Rubiolo

Sánchez

et al. 2021

Genes

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The neural crest is a multipotent cell population that develops from the dorsal neural fold of vertebrate embryos in order to migrate extensively and differentiate into a variety of tissues. A number of gene regulatory networks coordinating neural crest cell specification and differentiation have been extensively studied to date. Although several publications suggest a common role for microRNA-145 (miR-145) in molecular reprogramming for cell cycle regulation and/or cellular differentiation, little is known about its role during in vivo cranial neural crest development. By modifying miR-145 levels in zebrafish embryos, abnormal craniofacial development and aberrant pigmentation phenotypes were detected. By whole-mount in situ hybridization, changes in expression patterns of col2a1a and Sry-related HMG box (Sox) transcription factors sox9a and sox9b were observed in overexpressed miR-145 embryos. In agreement, zebrafish sox9b expression was downregulated by miR-145 overexpression. In silico and in vivo analysis of the sox9b 3′UTR revealed a conserved potential miR-145 binding site likely involved in its post-transcriptional regulation. Based on these findings, we speculate that miR-145 participates in the gene regulatory network governing zebrafish chondrocyte differentiation by controlling sox9b expression.

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Section: Discussionsupporting

confidence: 92%

Conservation of Zebrafish MicroRNA-145 and Its Role during Neural Crest Cell Development

Steeman

Rubiolo

Sánchez

et al. 2021

Genes

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“…In OC, YTHDF1 (reader) facilitates the expression of EIF3C [5] and the stem cell-like phenotype of cisplatin resistance [6] in a m6A-dependent manner, thereby strengthening tumorigenesis and metastasis. ALKBH5 (eraser) [7] and YTHDF2 (reader) [8,9] were shown to regulate the carcinogenesis of OC by modulating m6A levels. IGF2BP1 (reader) was demonstrated to augment the translation of serum response factor through m6A modification [10].…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer

et al. 2021

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Background Both N6-methyladenosine (m6A) modification and lncRNAs play an important role in the carcinogenesis and cancer inhibition of ovarian cancer (OC). However, lncRNAs involved in m6A regulation (LI-m6As) have never been reported in OC. Herein, we aimed to identify and validate a signature based on LI-m6A for OC. Methods RNA sequencing profiles with corresponding clinical information associated with OC and 23 m6A regulators were extracted from TCGA. The Pearson correlation coefficient (PCC) between lncRNAs and 23 m6A regulators (|PCC|> 0.4 and p < 0.01) was calculated to identify LI-m6As. The LI-m6As with significant prognostic value were screened based on univariate Cox regression analysis to construct a risk model by LASSO Cox regression. Gene Set Enrichment Analysis (GSEA) was implemented to survey the biological functions of the risk groups. Several clinicopathological characteristics were utilized to evaluate their ability to predict prognosis, and a nomogram was constructed to evaluate the accuracy of survival prediction. Besides, immune microenvironment, checkpoint, and drug sensitivity in the two risk groups were compared using comprehensive algorithms. Finally, real-time qPCR analysis and cell counting kit-8 assays were performed on an alternative lncRNA, CACNA1G-AS1. Results The training cohort involving 258 OC patients and the validation cohort involving 111 OC patients were downloaded from TCGA. According to the PCC between the m6A regulators and lncRNAs, 129 LI-m6As were obtained to perform univariate Cox regression analysis and then 10 significant prognostic LI-m6As were identified. A prognostic signature containing four LI-m6As (AC010894.3, ACAP2-IT1, CACNA1G-AS1, and UBA6-AS1) was constructed according to the LASSO Cox regression analysis of the 10 LI-m6As. The prognostic signature was validated to show completely opposite prognostic value in the two risk groups and adverse overall survival (OS) in several clinicopathological characteristics. GSEA indicated that differentially expressed genes in disparate risk groups were enriched in several tumor-related pathways. At the same time, we found significant differences in some immune cells and chemotherapeutic agents between the two groups. An alternative lncRNA, CACNA1G-AS1, was proven to be upregulated in 30 OC specimens and 3 OC cell lines relative to control. Furthermore, knockdown of CACNA1G‐AS1 was proven to restrain the multiplication capacity of OC cells. Conclusions Based on the four LI-m6As (AC010894.3, ACAP2-IT1, CACNA1G-AS1, and UBA6-AS1), the risk model we identified can independently predict the OS and therapeutic value of OC. CACNA1G‐AS1 was preliminarily proved to be a malignant lncRNA.

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“…Our previous findings confirmed that miR-145 inhibited ovarian cancer growth in vivo and in vitro [ 12 ]. MiR-145 blocked epithelial-mesenchymal transition of ovarian cancer cells by targeting FSCN1 [ 12 ], inhibited glutamine metabolism by targeting c-myc [ 14 ], inhibited the Warburg effect by targeting HK2 [ 16 ], and regulated RNA methylation by targeting YTHDF2 [ 24 ]. In order to test whether miR-145 was involved in the regulation of mitochondrial function, we then detected mitochondrial biogenesis by assessing the mtDNA copy number, ATP production, mitochondrial membrane potential, and mitochondrial-associated protein expression levels.…”

Section: Discussionmentioning

confidence: 99%

miR-145 inhibits mitochondrial function of ovarian cancer by targeting ARL5B

et al. 2021

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Metabolic reprogramming refers to the transformation of the whole metabolic network including glycolysis and mitochondrial metabolism, mainly manifested in Warburg effect and mitochondrial metabolic reprogramming. The roles of miR-145 in glycolysis have been established in ovarian cancer cells. Howerer, its roles in mitochondrial metabolic reprogramming are still unclear. This study aims to identify whether miR-145 regulates mitochondrial metabolic reprogramming in ovarian cancer cells. First, functional experiment showed that overexpression of miR-145 inhibited mitochondrial function in ovarian cancer cells, evident by the decreased mtDNA copy numbers, ATP level, mitochondrial membrane potential, and the expression levels of mitochondrial markers. Mechanistically, miR-145 inhibited mitochondrial function by targeting ARL5B directly. Futhermore, miR-145 overexpression decreased ARL5B expression in ovarian cancer tissue subcutaneous tumors of nude mice. In conclusion, we have highlighted that miR-145 inhibits mitochondrial function and achieves this by targeting ARL5B directly for the first time. The results provides a more adequate theoretical basis for understanding the molecular pathology of ovarian cancer, and provides the necessary basic data for miR-145 as a potential diagnosis and treatment target for ovarian cancer.

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YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

Cited by 62 publications

References 27 publications

Conservation of Zebrafish MicroRNA-145 and Its Role during Neural Crest Cell Development

Conservation of Zebrafish MicroRNA-145 and Its Role during Neural Crest Cell Development

Identification and validation of lncRNAs involved in m6A regulation for patients with ovarian cancer

miR-145 inhibits mitochondrial function of ovarian cancer by targeting ARL5B

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