MiR-324-3p promotes tumor growth through targeting DACT1 and activation of Wnt/β-catenin pathway in hepatocellular carcinoma

Tuo, Hang; Wang, Yufeng; Wang, Liang; Yao, Bowen; Li, Qing; Liu, Zhikui; Han, Shaoshan; Yin, Guowen; Tu, Kangsheng; Liu, Qingguang

doi:10.18632/oncotarget.20058

Cited by 48 publications

(37 citation statements)

References 27 publications

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“…Previous studies have found that miRNAs promote HCC invasion and metastasis via the Wnt/β-catenin signaling pathway (28,29). The results of the present study demonstrated that overexpression of miR-2053 resulted in a reduction in Wnt3 protein levels.…”

Section: Mir-2053 Inhibits Activation Of the Wnt/β-catenin Signaling supporting

confidence: 67%

MicroRNA‑2053 overexpression inhibits the development and progression of hepatocellular carcinoma

Song

Zhao

et al. 2019

Oncol Lett

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MicroRNAs (miRNAs) represent a class of small RNAs that participate in the regulation of tumor progression. However, the identification of functional miRNAs in tumors has not been thoroughly elucidated. In the present study we aim to investigate the impact of altered miR-2053 expression in hepatocellular carcinoma (HCC) cells. The results of the present study demonstrated that miR-2053 overexpression inhibited cell proliferation, migration and invasion, and promoted apoptosis in a HCC cell line, while miR-2053 knockdown induced the opposite cellular phenotypic changes. Mechanistically, it was found that overexpression of miR-2053 resulted in the downregulation of the phosphoinositide 3-kinase (PI3K) and Wnt/β-catenin signaling pathways, which are aberrantly expressed in HCC. Collectively, the results indicate that miR-2053 serves as a tumor suppressor with a crucial role in inhibiting the proliferation, migration and invasion of HCC via targeting the PI3K and Wnt/β-catenin signaling pathways. These data indicate a potential application of miR-2053 in cancer therapy.

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Section: Mir-2053 Inhibits Activation Of the Wnt/β-catenin Signaling supporting

confidence: 67%

MicroRNA‑2053 overexpression inhibits the development and progression of hepatocellular carcinoma

Song

Zhao

et al. 2019

Oncol Lett

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“…We did not observe a correlation between the number of potential target genes for a miRNA and the number of cohorts where it is predicted ( Figure S20). All these miRNAs are derived from precursors of already established oncomiRs or tumor suppressor miRNAs, or known to be involved in immune response or inflammation [50][51][52][53][54][55][56][57][58][59][60][61]. Note that hsa-miR-17-3p, hsa-miR-17-5p, hsa-miR-18a-3p, hsa-miR-18a-3p, hsa-miR-20a-3p, hsa-miR-20a-5p, and hsa-miR-92a-1-5p are part of a single miRNA cluster on chromosome 13 and this polycistronic cluster (known as miR-17-92) is well known to be composed of oncomiRs involved in proliferation and tumor angiogenesis, and reducing apoptosis of cancer cells [50].…”

Section: Combining Transcriptional and Post-transcriptional Regulatiomentioning

confidence: 99%

Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of the gene regulatory program in cancers

Castro-Mondragón

Aure

Lingærde

et al. 2020

Preprint

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Background: Most cancer alterations occur in the noncoding portion of the human genome, which contains important regulatory regions acting as genetic switches to ensure gene expression occurs at correct times and intensities in correct tissues. However, large scale discovery of noncoding events altering the gene expression regulatory program has been limited to a few examples with high recurrence or high functional impact. Results:We focused on transcription factor binding sites (TFBSs) that show similar mutation loads than what is observed in protein-coding exons. By combining cancer somatic mutations in TFBSs and expression data for protein-coding and miRNA genes, we evaluated the combined effects of transcriptional and post-transcriptional alteration on the dysregulation of the regulatory programs in cancer. The analysis of seven cancer cohorts culminated with the identification of protein-coding and miRNA genes linked to mutations at TFBSs that were associated with a cascading trans-effect deregulation on the cells' regulatory program. Our analyses of cisregulatory mutations associated with miRNAs recurrently predicted 17 miRNAs as pan-cancerassociated through deregulation of their target gene networks. Overall, our predictions were enriched for protein-coding and miRNA genes previously annotated as cancer drivers. Functional enrichment analyses highlighted that cis-regulatory mutations are associated with the dysregulation of key pathways associated with carcinogenesis Conclusions: These pan-cancer results suggest that our method predicts cis-regulatory mutations related to the dysregulation of key gene regulatory networks in cancer patients. It highlights how the gene regulatory program is disrupted in cancer cells by combining transcriptional and post-transcriptional regulation of gene expression.At the post-transcriptional level, miRNAs control gene expression by acting as 'buffers' to induce translational repression and mRNA degradation [28,29]. miRNA biogenesis generally comprises

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“…72 Strand selection is mainly determined by two rules involving 73 thermodynamic characteristics and 5 ′ nucleotide identity of a miRNA 74 duplex. The crystal structures of human AGO and its homologues have 75 highlighted a key role of a basic pocket of the MID domain that interacts 76 with the mono-phosphorylated 5 ′ end of the guide strand ( Thermodynamically unstable 5 ′ ends would be more readily accessible 79 to the pocket, leading to the preference for unstable 5 ′ ends by AGO 80 (Khvorova et al, 2003;Schwarz et al, 2003). Furthermore, analyses of 81 4/51 miRNA sequences indicated that there is a clear bias for U or A at the 5 ′ 82…”

Section: Introductionmentioning

confidence: 99%

MicroRNA arm switching regulated by uridylation

Kim

et al. 2020

Preprint

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1Strand selection is a critical step in microRNA (miRNA) biogenesis. 2Although the dominant strand may alter depending on cellular contexts, 3 the molecular mechanism and physiological significance of such 4 alternative strand selection (or "arm switching") remain elusive. Here we 5 find mir-324 as one of the strongly regulated miRNAs by arm switching, 6 and identify terminal uridylyl transferases TUT4 and TUT7 as the key 7 regulators. Uridylation of pre-mir-324 by TUT4/7 re-positions DICER on 8 the pre-miRNA and shifts the cleavage site. This alternative processing 9 produces a duplex with a different terminus, from which the 3 ′ strand (3p) 10 is selected instead of the 5 ′ strand (5p). In glioblastoma, the TUT4/7 and 11 3p levels are upregulated while the 5p level is reduced. Manipulation of 12 the strand ratio is sufficient to impair glioblastoma cell proliferation. This 13 study uncovers a role of uridylation as a molecular switch in alternative 14 strand selection and implicates its therapeutic potential. Keywords16 miRNA, miRNA biogenesis, arm switching, strand selection, miRNA 17 tailing, uridylation, TUTase, DICER, miR-324, glioblastoma 18 2/51 103In this study, we aimed to identify miRNAs that undergo conserved arm 104 switching and uncover its molecular mechanism. We find that mir-324 is 105 the most prominently regulated miRNA through arm switching and that 106 the arm switching is actively controlled by uridylation enzymes. 107 RESULTS 108Arm switching of miR-324 109 In order to gain molecular insights into miRNA arm switching, we first 110 searched for miRNAs that exhibit significant alterations in their strand 111 5/51We are grateful to Eunji Kim for cloning and mutagenesis of expression 685 constructs. We also thank Yoonseok Jung, Dongwan Kim, Hyunjoon 686

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MiR-324-3p promotes tumor growth through targeting DACT1 and activation of Wnt/β-catenin pathway in hepatocellular carcinoma

Cited by 48 publications

References 27 publications

MicroRNA‑2053 overexpression inhibits the development and progression of hepatocellular carcinoma

MicroRNA‑2053 overexpression inhibits the development and progression of hepatocellular carcinoma

Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of the gene regulatory program in cancers

MicroRNA arm switching regulated by uridylation

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