However, the signaling mechanism underlying PTEN-mediated antitumor effect remains largely unknown, and the crosstalk between PTEN and CXCR4 in OS has not been investigated.
In summary, our data support a critical role for NF-κB-dependent upregulation of miR-181b, which further inhibited PTEN expression and promoted the cell proliferation of OS cell lines.
Overall, the results revealed that miR-29, as a tumor promoter, is involved in OS progression and metastasis by targeting PTEN, indicating that the miR-29/PTEN pathway is a potential therapeutic target for the treatment of OS.
Moreover, TSC01682 treatment in osteosarcoma cells also caused a decrease of other CRL4B components including CUL4-associated factor 11 (DCAF11) and DCAF13, but an increase of two CRL4B substrates including cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through inhibiting their ubiquitination.
Therefore, circ_ORC2 binds with miR-19a and enhances its expression, thereby inhibiting downstream PTEN expression and activating Akt pathway to promote osteosarcoma cell growth and invasion.
In conclusion, the results of the present study indicate that the expression of miRNA-21, PI3K and AKT is increased in the osteosarcoma cell line MG-63, which results in reduced expression of PTEN and increased expression of proteins in the PI3K/AKT signaling pathway, and thus increases the aggressiveness of osteosarcoma cells.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a positive regulatory role on cell autophagy through inhibiting PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. miR-155 plays a critical role in osteosarcoma occurrence and chemoresistance.
To conclude, our integrated approach demonstrates that UCA1 confers a tumor promoter function by promoting cell proliferation and silencing of the PTEN/AKT signaling pathway in osteosarcoma.
Serum miRNA-21 may be used to effectively diagnose osteosarcoma and predict the prognosis of the disease. miRNA-21 knockdown inhibited the proliferation of osteosarcoma and promoted the expression of PTEN and TGF-β1 proteins in the osteosarcoma cells.
We report a patient with CS presenting with ganglioneuromatosis, benign breast mass and osteosarcoma, harboring a novel molecular alteration in PTEN which to our knowledge has not been previously reported.
MiR-524 induces the proliferation of osteosarcoma cells through activation of the PI3K/AKT pathway via inhibition of the target gene PTEN, which provides a theoretical basis for selecting a new therapeutic target for osteosarcoma.
In addition, we indicated that ectopic expression of CASC2 suppressed miR-181a expression and enhanced the expression of Ras association domain family member 6 (RASSF6), PTEN and ATM in osteosarcoma cell, which were the direct target gene of miR-181a.
In this study, we first examined the expression of SIX1 and PTEN in human osteosarcoma tissues or blood samples and cell lines by immunohistochemistry, western blot analysis and qPCR.
Equally importantly, PTEN is the most significant negative regulator of PI3K/Akt signaling cascade, the constitutively activated pathway in osteosarcoma.
We investigated the role of nuclear factor-κB (NF-κB) and phosphatase and tensin homolog deleted in chromosome 10 (PTEN) in the pathogenesis of osteosarcoma and its relationship with prognosis.
We then treated previously reported mouse OS tumor cells MOTO-Rank<sup>Δ/ΔOC</sup> and human OS cell line U2OS with PTEN inhibitor VO-OHpic to investigate how PTEN impacts tumor cell behaviors.
Besides, miR-23a-mediated suppression of PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition (EMT) in osteosarcoma cells, and finally enhanced the activity of osteosarcoma cell proliferation and movement and promoted osteosarcoma xenograft tumor growth in mouse models.