MicroRNA-874–mediated inhibition of the major G1/S phase cyclin, CCNE1, is lost in osteosarcomas

Ghosh, Tanushree; Varshney, Akhil; Kumar, Praveen; Kaur, Manpreet; Kumar, Vipin; Shekhar, Ritu; Devi, Raksha; Priyanka, Priyanka; Khan, Md. Muntaz; Saxena, Sandeep

doi:10.1074/jbc.m117.808287

Cited by 28 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data of RT-qPCR analysis indicated that miR-874 (23,24). miR-874 expression is also downregulated in osteosarcoma tissues and cell lines (25,26). Low miR-874 expression is strongly related to TNM stage, tumour size and lymph node metastasis in patients with osteosarcoma (26).…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

MicroRNA‑874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin

2018

View full text Add to dashboard Cite

MicroRNAs (miRNAs/miRs) serve important roles in regulating gene expression by directly binding to the 3'‑untranslated regions of target genes. Multiple miRNAs are dysregulated in retinoblastoma (RB) and their dysregulation is closely related to RB malignancy. Therefore, exploring the detailed roles of miRNAs in RB is valuable to facilitate the development of effective therapeutic targets for patients with this disease. miRNA‑874‑3p (miR‑874) has been recently reported to be downregulated in several types of human cancer and serves an essential role in cancer progression. However, the expression pattern and detailed roles of miR‑874 in RB, as well as the underlying molecular mechanisms in RB, have not been clearly elucidated. Therefore, this study detected miR‑874 expression in RB tissues and cell lines. The biological roles of miR‑874 in RB were determined and the underlying mechanisms of its actions in RB cells were also examined. This study revealed that miR‑874 expression was aberrantly underexpressed in RB tissues and cell lines. However, returning miR‑874 expression restricted the proliferative and invasive abilities of RB cells. In terms of the underlying mechanism, metadherin (MTDH) was validated as a direct target gene of miR‑874 in RB cells. MTDH inhibition could imitate the inhibitory roles of miR‑874 overexpression in RB cells. Furthermore, forced MTDH expression partially reversed the suppressive effects of miR‑874 on RB cells. In conclusion, this study revealed that miR‑874 may inhibit RB progression by directly targeting MTDH. Restoration of miR‑874 expression may be a novel strategy for preventing the rapid growth and metastasis of RB cells.

show abstract

Section: Discussionmentioning

confidence: 97%

“…In osteosarcoma, miR-874 upregula-. In osteosarcoma, miR-874 upregulation represses cell proliferation, migration and invasion, promotes cell apoptosis in vitro and inhibits tumour growth in vivo (25,26). In breast cancer, ectopic miR-874 expression restricts cell proliferation, increases apoptosis and induces cell cycle arrest (30).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin

2018

View full text Add to dashboard Cite

show abstract

“…miR-874 has been implicated in the regulation of cancer initiation and progression. For instance, resumption expression of miR-874 suppressed osteosarcoma cell growth and metastasis, increased apoptosis in vitro and reduced tumour growth in vivo (27,34). Numerous studies have indicated that miR-874 upregulation inhibited cell proliferation, induced apoptosis and reversed chemoresistance in colorectal cancer (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑874 inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells by directly targeting paired box 6

Diao

Cao

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

Studies have demonstrated that a number of microRNAs (miRNAs) are dysregulated in pancreatic ductal adenocarcinoma (PDAC), and alterations in their expression may affect the onset and progression of PDAC. Therefore, the expression patterns, biological functions and associated molecular mechanisms of miRNAs in PDAC should be elucidated for the development of novel therapeutic methods. Previous studies reported significant miRNA‑874 (miR‑874) dysregulation in multiple types of human cancer. However, the expression pattern, possible roles and underlying mechanisms of miR‑874 in PDAC remain to be elucidated. This study evaluated miR‑874 expression in PDAC and examined its biological functions and underlying mechanism of action in PDAC progression. miR‑874 expression was downregulated in PDAC tissues and cell lines. Functional experiments demonstrated that upregulation of miR‑874 inhibited cell proliferation and invasion in PDAC. Additionally, paired box 6 (PAX6) was predicted as a putative target of miR‑874 using bioinformatics analysis. Further experiments demonstrated that PAX6 may be the direct target gene of miR‑874 in PDAC. PAX6 knockdown exhibited similar inhibitory effects to miR‑874 overexpression in PDAC cells. In addition, restored PAX6 expression may reverse the suppressive roles of miR‑874 overexpression in PDAC cells. The results demonstrated that miR‑874 may serve tumor suppressive roles in PDAC by directly targeting PAX6. Therefore, miR‑874 may exhibit potential applications for treatment of patients with PDAC.

show abstract

“…Total RNA was extracted from cells using TRIzol reagent (Invitrogen) and reverse-transcribed into cDNA using Moloney murine leukemia virus reverse transcriptase (Invitrogen). For miRNA analysis, total RNA was poly(A)-tailed using Escherichia coli poly(A) polymerase (New England Biolabs) before reverse transcription as described previously (6). The qRT-PCR reactions were carried out in duplicates in a 10-l volume for the expression analysis.…”

Section: Rna Extraction and Quantitative Real-time Pcrmentioning

confidence: 99%

The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression

Shekhar

Priyanka

Kumar

et al. 2019

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Ronald C. WekMicroRNAs of the miR-16 and miR-34 families have been reported to inhibit cell cycle progression, and their loss has been linked to oncogenic transformation. Utilizing a high-throughput, genome-wide screen for miRNAs and mRNAs that are differentially regulated in osteosarcoma (OS) cell lines, we report that miR-449a and miR-424, belonging to the miR-34 and miR-16 families, respectively, target the major S/G 2 phase cyclin, cyclin A2 (CCNA2), in a bipartite manner. We found that the 3-UTR of CCNA2 is recognized by miR-449a, whereas the CCNA2 coding region is targeted by miR-424. Of note, we observed loss of both miR-449a and miR-424 in OS, resulting in derepression of CCNA2 and appearance of aggressive cancer phenotypes. Ectopic expression of miR-449a and miR-424 significantly decreased cyclin A2 levels and inhibited proliferation rate, migratory potential, and colony-forming ability of OS cells. To further probe the roles of miR-449a and miR-424 in OS, we developed an OS mouse model by intraosseous injection of U2OS cells into the tibia bone of NOD-scid mice, which indicated that miR-449a and miR-424 co-expression suppresses tumor growth. On the basis of this discovery, we analyzed the gene expression of human OS biopsy samples, revealing that miR-449a and miR-424 are both down-regulated, whereas cyclin A2 is significantly up-regulated in these OS samples. In summary, the findings in our study highlight that cyclin A2 repression by miRNAs of the miR-16 and miR-34 families is lost in aggressive OS.

show abstract

MicroRNA-874–mediated inhibition of the major G1/S phase cyclin, CCNE1, is lost in osteosarcomas

Cited by 28 publications

References 45 publications

MicroRNA‑874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin

MicroRNA‑874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin

MicroRNA‑874 inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells by directly targeting paired box 6

The microRNAs miR-449a and miR-424 suppress osteosarcoma by targeting cyclin A2 expression

Contact Info

Product

Resources

About