miR-181a-5p, an inducer of Wnt-signaling, facilitates cell proliferation in acute lymphoblastic leukemia

Lyu, Xiaoming; Li, Jinbang; Xi, Yun; Huang, Rui; Deng, Xubin; Wang, Ying‐Ping; Chen, Youming; Xiao, Gang

doi:10.3892/or.2017.5425

Cited by 39 publications

(31 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…miR‐342‐3p has not previously been associated with OS in miRNA profiling studies. miR‐181a‐5p has been shown to downregulate a Wnt antagonist, thereby activating the Wnt signaling, which is, as described above, important for the differentiation of osteoprecursor cells into OB cells (Lyu et al ., ).…”

Section: Discussionmentioning

confidence: 97%

miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

et al. 2017

View full text Add to dashboard Cite

Osteosarcoma (OS) is an aggressive bone tumor primarily affecting children and adolescents. The etiology of OS is not fully understood. Thus, there is a great need to obtain a better understanding of OS development and progression. Alterations in miRNA expression contribute to the required molecular alterations for neoplastic initiation and progression. This study is the first to investigate miRNA expression in OS in a large discovery and validation cohort comprising a total of 101 OS samples. We established the signature of altered miRNA expression in OS by profiling the expression level of 752 miRNAs in 23 OS samples using sensitive LNA‐enhanced qPCR assays. The identified miRNA expression changes were correlated with gene expression in the same samples. Furthermore, miRNA expression changes were validated in a second independent cohort consisting of 78 OS samples. Analysis of 752 miRNAs in the discovery cohort led to the identification of 33 deregulated miRNAs in OS. Twenty‐nine miRNAs were validated with statistical significance in the second cohort comprising 78 OS samples. miRNA/mRNA targets were determined, and 361 genes with an inverse expression of the target miRNA were identified. Both the miRNAs and the identified target genes were associated with multiple pathways related to cancer as well as bone cell biology, thereby correlating the deregulated miRNAs with OS tumorigenesis. An analysis of the prognostic value of the 29 miRNAs identified miR‐221/miR‐222 to be significantly associated with time to metastasis in both cohorts. This study contributes to a more profound understanding of OS tumorigenesis, by substantiating the importance of miRNA deregulation. We have identified and validated 29 deregulated miRNAs in the – to our knowledge – largest discovery and validation cohorts used so far for miRNA analyses in OS. Two of the miRNAs showed a promising potential as prognostic biomarkers for the aggressiveness of OS.

show abstract

Section: Discussionmentioning

confidence: 97%

miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Xin et al 27 have indicated that Dishevelled-Axin domain-containing 1 could promote acute myeloid leukemia cells growth via regulating Wnt/βcatenin pathway. Lyu et al 28 suggested that miR-181a-5p could facilitate cell proliferation in ALL by activating Wnt/ β-catenin pathway. In addition, cyclin D1 is necessary for the progression of the cell cycle, and its overexpression has Figure 7 GAS2 activated Wnt/β-catenin pathway in Jurkat and CCRF-CEM cells.…”

Section: Discussionmentioning

confidence: 99%

<p>GAS2 Promotes Cell Proliferation and Invasion and Suppresses Apoptosis in Pediatric T-Cell Acute Lymphoblastic Leukemia and Activates Wnt/β-Catenin Pathway</p>

Kong¹,

Zhao²,

Tian³

et al. 2020

OTT

View full text Add to dashboard Cite

Purpose: This study aimed to investigate the effect of growth arrest specific 2 (GAS2) on T-cell acute lymphoblastic leukemia (T-ALL) and its potential molecular mechanism. Methods: The GAS2 expression level was detected by qRT-RCR and Western blot in normal T lymphocytes and TALL cells Jurkat and CCRF-CEM. The proliferation and invasion of Jurkat and CCRF-CEM cells were detected by MTT and Transwell assay, respectively. Apoptosis and cell cycle were measured by flow cytometry. In addition, the chemotherapeutic sensitivity of Jurkat and CCRF-CEM cells was measured MTT assay and flow cytometry. Results: GAS2 was highly expressed in Jurkat and CCRF-CEM cells. GAS2 could promote cell proliferation and invasion, and inhibit apoptosis of Jurkat and CCRF-CEM cells. GAS2 also promoted cell cycle changes from G0/G1 phase to S phase in Jurkat and CCRF-CEM cells. In addition, GAS2 could reduce the chemotherapeutic sensitivity of Jurkat and CCRF-CEM cells. GAS2 overexpression could promote the expression levels of ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, c-myc, cyclin D1 and β-catenin, while GAS2 knockdown could inhibit their expression levels. Meanwhile, GAS2 overexpression could inhibit Bax expression. Moreover, Wnt/β-catenin pathway inhibitor XAV939 could inhibit the expressions of c-myc, cyclin D1 and β-catenin, but activator LiCl could promote their expression. Conclusion: Our study demonstrated that GAS2 could promote cell proliferation and invasion, and induce cell cycle, as well as inhibit apoptosis and could activate the Wnt/βcatenin pathway in TALL cells.

show abstract

“…The downregulation of WIF1 could activate Wnt/β‐catenin signaling to promote cell proliferation (Lyu et al . ). We thus suggest that the nonconservative substitution probably alters WIF1 interactivity with protein partners and consequently affects gene function.…”

Section: Mutations Identified In Wif1 and Hmga2 Genesmentioning

confidence: 97%

Molecular cloning of WIF1 and HMGA2 reveals ear‐preferential expression while uncovering a missense mutation associated with porcine ear size in WIF1

et al. 2019

View full text Add to dashboard Cite

Considerable diversity exists in porcine ear size, which is an important morphological feature of pig breeds. Previously, we localized four crucial candidate genes-high mobility group AT-hook 2 (HMGA2), LEM domain-containing 3 (LEMD3), methionine sulfoxide reductase B3 (MSRB3) and Wnt inhibitory factor 1 (WIF1)-on Sus Scrofa chromosome 5 affecting porcine ear size, then cloned LEMD3 and MSBR3. In this study, we performed rapid amplification of cDNA ends to obtain full-length cDNA sequences of 2338-bp WIF1 and 2998-bp HMGA2. Using quantitative real-time PCR, we revealed that WIF1 expression was highest in ear cartilage of 60-day-old pigs and that this is therefore a better candidate gene for ear size than HMGA2. We further screened coding sequence variants in both genes and identified only one missense mutation (WIF1: c.1167C>G) in a conserved epidermal growth factor-like domain from the mammalian WIF1 protein. The protein-altering mutation was significantly associated with ear size across the Large White 9 Minzhu hybrid and Beijing Black pig populations. When WIF1:c.1167C>G was included as fixed effect in the model to re-run a genome-wide association study in the Large White 9 Minzhu intercross population the P-value of the peak SNP on SSC5 from re-running the genome-wide association study dropped from 2.45E-12 to 7.33E-05. Taken together, the WIF1:c.1167C>G could be an important mutation associated with ear size. Our findings provide helpful information for further studies of the molecular mechanisms controlling porcine ear size.

show abstract

miR-181a-5p, an inducer of Wnt-signaling, facilitates cell proliferation in acute lymphoblastic leukemia

Cited by 39 publications

References 47 publications

miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

<p>GAS2 Promotes Cell Proliferation and Invasion and Suppresses Apoptosis in Pediatric T-Cell Acute Lymphoblastic Leukemia and Activates Wnt/β-Catenin Pathway</p>

Molecular cloning of WIF1 and HMGA2 reveals ear‐preferential expression while uncovering a missense mutation associated with porcine ear size in WIF1

Contact Info

Product

Resources

About