miR‐522 stimulates TGF‐β/Smad signaling pathway and promotes osteosarcoma tumorigenesis by targeting PPM1A

Xu, Xiao; Liu, Mengmeng

doi:10.1002/jcb.29160

Cited by 17 publications

(9 citation statements)

References 33 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, accumulating evidence has demonstrated that the TGFβ/SMAD pathway is involved in OS progression. For instance, miR-522 promotes osteosarcoma tumorigenesis by targeting PPM1A via the TGF-β/SMAD signaling pathway (Xu and Liu, 2019). In addition, GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF-β signaling pathway .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-β/SMAD Signaling Pathway and Upregulating SSH2 Expression

Zheng

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Osteosarcoma (OS), a frequent malignant tumor which mainly occurs in the bone. The roles of long noncoding RNAs (lncRNAs) have been revealed in cancers, including OS. LncRNA long intergenic non-protein coding RNA (LINC00174) has been validated as an oncogene in several cancers. However, the role of LINC00174 in OS has not been explored. In our research, loss-of-function assays were conducted to explore the function of LINC00174 in OS cells. Then, we explored the downstream pathway of LINC00174 in OS cells. Bioinformatics, RNA pull-down and RIP experiments investigated the downstream mechanism of LINC00174 in OS cells. Finally, in vivo assays clarified the effect of LINC00174 on tumorigenesis. We found that LINC00174 was upregulated in OS tissues and cells. LINC00174 knockdown repressed OS cell growth. Mechanistically, LINC00174 knockdown suppressed the TGF-β/SMAD pathway. LINC00174 interacted with miR-378a-3p, and slingshot protein phosphatase 2 (SSH2) 3′UTR was targeted by miR-378a-3p in OS cells. Rescue assays showed that SSH2 upregulation or miR-378a-3p inhibition counteracted the inhibitory effect of LINC00174 depletion in OS cell growth. Additionally, LINC00174 depletion suppressed tumor growth in mice. In conclusion, LINC00174 promotes OS cellular malignancy and tumorigenesis via the miR-378a-3p/SSH2 axis and the TGF-β/SMAD pathway, which might provide a novel insight for OS treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED: LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-β/SMAD Signaling Pathway and Upregulating SSH2 Expression

Zheng

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…Recent evidence has illustrated that numerous miRNAs are dysregulated in osteosarcoma and serve as an oncogene or tumor suppressor ( 13 , 26 ). Here, miR-487a was significantly upregulated in osteosarcoma cells and tissue.…”

Section: Discussionmentioning

confidence: 99%

KLF5‑induced miR‑487a augments the progression of osteosarcoma cells by targeting NKX3‑1 in vitro

2022

View full text Add to dashboard Cite

MicroRNAs (miRNAs or miRs) are involved in the development and progression of numerous types of cancer however their role in osteosarcoma has not been fully clarified. The present study aimed to use high-throughput bioinformatics analysis as well as in vitro experiments to investigate the potential role of transcription factors, miRNAs and their targets in the progression of osteosarcoma. miRNA data and clinical information of osteosarcoma were obtained from Gene Expression Omnibus database to investigate differentially expressed miRNAs. The expression of miRNAs/mRNAs in osteosarcoma cell lines was detected via reverse transcription-quantitative (RT-qPCR). MTT and colony formation assay were used to determine cell proliferation ability and transwell assay was used to observe cell invasion and migration ability. A total of four prediction algorithms for miRNA-mRNA interactions were used to determine potential target genes of miR-487a. Predicted target genes were used to intersect with overlapped differentially expressed genes (DEGs) from GSE12865 and The Cancer Genome Atlas osteosarcoma datasets. Expression of NK3 homeobox 1 (NKX3-1) was analyzed by western blotting and RT-qPCR assay. Dual luciferase assay was conducted to verify whether NKX3-1 was a direct target of miR-487a. The regulatory association between Kruppel-like factor 5 (KLF5) and miR-487a was detected using chromatin immunoprecipitation assay. miR-487a was upregulated in osteosarcoma tissue (GSE65071 and GSE28423) and cell lines (HOS and MG63). miR-487a mimic promoted proliferation, migration and invasion of osteosarcoma cells. NKX3-1 was a direct target of miR-487a and transfection of NKX3-1 plasmid reversed the effect of miR-487a on proliferation, migration and invasion of osteosarcoma cells. KLF5 enhanced miR-487a expression by directly binding to its promoter region and miR-487a inhibitor reversed the effect of KLF5 on proliferation, migration and invasion of osteosarcoma cells. The present results indicated that KLF5/miR-487a signaling promoted invasion and metastasis of osteosarcoma cells via targeting NKX3-1.

show abstract

“…Several experimentally validated targets of miR-522 in human cancers have been documented, including ABCB5, BLM, MAOB, PHLPP1, DKK1, SFRP2, DENND2D, SOCS5 and PPM1A [20,[23][24][25][26][29][30][31]45]. PTGR1 and SOCS3 are reported to be regulated by miR-522 to participate into the inflammation processes [35,36].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting of ΔNp63α by miR‐522 promotes the migration of breast epithelial cells

et al. 2021

View full text Add to dashboard Cite

The TP63 gene, which encodes the p63 protein, is involved in multiple biological processes, including embryonic development and tumorigenesis. ΔNp63α, the predominant isoform of p63 in epithelial cells, acts as an oncogene in early‐stage tumors, but paradoxically acts as a potent antimetastatic factor in advanced cancers. Here, we report that ΔNp63α is a direct target of hsa‐miR‐522 (miR‐522). Induced expression of miR‐522 reduced the levels of ΔNp63α, predisposing breast epithelial cells to a loss of epithelial and acquisition of mesenchymal morphology, resulting in accelerated collective and single‐cell migration. Restoration of ΔNp63α repressed miR‐522‐induced migration. Interestingly, overexpression of miR‐522 did not affect breast epithelial cell proliferation, suggesting that miR‐522 acts specifically through ΔNp63α in this context. Furthermore, expression of miR‐522‐3p and p63 was negatively correlated in human cancer samples. Thus, miR‐522 might be a causative factor for breast tumorigenesis and cancer metastasis. In summary, our results reveal a novel miR‐522/p63 axis in cell migration and thus suggest a potential strategy for therapeutic treatment of cancer metastasis.

show abstract

miR‐522 stimulates TGF‐β/Smad signaling pathway and promotes osteosarcoma tumorigenesis by targeting PPM1A

Cited by 17 publications

References 33 publications

RETRACTED: LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-β/SMAD Signaling Pathway and Upregulating SSH2 Expression

RETRACTED: LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-β/SMAD Signaling Pathway and Upregulating SSH2 Expression

KLF5‑induced miR‑487a augments the progression of osteosarcoma cells by targeting NKX3‑1 in vitro

Targeting of ΔNp63α by miR‐522 promotes the migration of breast epithelial cells

Contact Info

Product

Resources

About