miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway

Xiao, Jie; Yu, Weifeng; Hu, Kai-Ming; Li, Maoqiang; Chen, Jianwei; Li, Zhanchun

doi:10.3892/or.2017.5484

Cited by 39 publications

(36 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PTEN is known to inhibit the activity of PI3K, which then affects the phosphorylation of Akt (12). The PI3K/PTEN/Akt signal pathway has been demonstrated to play a role in a variety of tumors including hematological neoplasms, liver cancer, intestinal cancer, osteosarcoma, and lymphoma (13)(14)(15)(16). This pathway was recently found to be closely related to chronic inflammatory diseases and autoimmune diseases such as asthma (17).…”

Section: Introductionmentioning

confidence: 99%

PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways

2017

View full text Add to dashboard Cite

Chronic rhinosinusitis (CRS) is a form of chronic inflammation of the nasal cavity and paranasal sinus with multi‑causal pathogenesis, including oxidative stress. Several lines of evidence have demonstrated that the phosphatase and tensin homolog gene (PTEN) can inhibit the activation of phosphoinositide 3‑kinase (PI3K) to affect phosphorylation of Akt. Importantly, the PI3K/PTEN/Akt signaling pathway is associated with various types of tumors, chronic inflammatory diseases, and autoimmune disease through its regulation of cell growth, apoptosis, proliferation, and metabolism. This in vitro study aimed to investigate the role of PTEN and the relationship between PTEN and the PI3K/Akt pathway in nasal epithelial cells under oxidative stress. H2O2 treatment was applied to induce a cell injury model of oxidative stress in rat nasal epithelial cells. Cells were divided into control, H2O2, H2O2+PTEN, and H2O2+siPTEN groups. Cell viability was measured using the CCK‑8 assay, and reactive oxygen species (ROS) levels and apoptosis rates were analyzed by flow cytometry (FCM). Oxidative parameters, including ROS, catalase (CAT), and malondialdehyde (MDA), were tested by enzyme‑linked immunosorbent assay (ELISA). The expression of apoptosis‑related genes and PI3K/Akt pathway was assayed by quantitative PCR (qPCR) and western blot. In H2O2‑injured cells, oxidative stress, due to increased ROS levels and apoptosis rates, was induced, and PTEN aggravated the injury. The levels of both p‑Akt and PTEN in H2O2‑injured cells were positively correlated and higher than in control cells. Unknown regulatory protein(s) may exist in the PI3K/PTEN/Akt pathway or the PTEN and PI3K/Akt pathways may be two independent signaling pathways that have cross interactions.

show abstract

Section: Introductionmentioning

confidence: 99%

PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways

2017

View full text Add to dashboard Cite

show abstract

“…In fact, down-regulation of miRNA92 in human plasma is a novel marker for acute leukemia patients [37]. Moreover, miRNA92a was observed to promote tumor growth of osteosarcoma by targeting the PTEN/AKT signaling pathway [38]. Additionally, deregulation of miRNA92a expression has been implicated in hepatocellular carcinoma [39], and, in breast cancer, estrogen receptor expression was reported to be regulated by miRNA92a [40].…”

Section: What Is the Biological Significance Of Mirna92a In Carcinogementioning

confidence: 99%

MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies miRNA92a as a Regulator of the LRIG1 Stem Cell Gene

Viswanathan

Opdenaker

Modarai

et al. 2020

IJMS

View full text Add to dashboard Cite

MicroRNAs (miRNAs) have a critical role in regulating stem cells (SCs) during development, and because aberrant expression of miRNAs occurs in various cancers, our goal was to determine if dysregulation of miRNAs is involved in the SC origin of colorectal cancer (CRC). We previously reported that aldehyde dehydrogenase (ALDH) is a marker for normal and malignant human colonic SCs and tracks SC overpopulation during colon tumorigenesis. MicroRNA expression was studied in ALDH-positive SCs from normal and malignant human colon tissues by Nanostring miRNA profiling. Our findings show that: (1) A unique miRNA signature distinguishes ALDH-positive CRC cells from ALDH-positive normal colonic epithelial cells, (2) Expression of four miRNAs (miRNA200c, miRNA92a, miRNA20a, miRNA93) are significantly altered in CRC SCs compared to normal colonic SCs, (3) miRNA92a expression is also upregulated in ALDH-positive HT29 CRC SCs as compared to ALDH-negative SCs, (4) miRNA92a targets the 3′UTR of LRIG1 SC gene, and (5) miRNA92a modulates proliferation of HT29 CRC cells. Thus, our findings indicate that overexpression of miRNA92a contributes to the SC origin of CRC. Strategies designed to modulate miRNA expression, such as miRNA92a, may provide ways to target malignant SCs and to develop more effective therapies against CRC.

show abstract

“…We also observed in COS-7 cells that pSer473 is dispensable for Akt1 signaling and phosphorylation of Thr308 alone was sufficient for maximal Akt1 signal prorogation. These results indicated Thr308 phosphorylation status is a superior biomarker for Akt1 activity [11] and called into question the frequent use of Ser473 phosphorylation as a diagnostic marker for Akt1 activity in cancer patients [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation-Dependent Inhibition of Akt1

Balasuriya¹,

McKenna²,

Liu³

et al. 2018

Preprint

View full text Add to dashboard Cite

Akt1 is a proto-oncogene that is over active in most cancers. Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473 further enhances catalytic activity. Akt1 activity is also regulated via interactions between the kinase domain and the N-terminal autoinhibitory pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1 in sitespecifically phosphorylated forms, the contribution of each activating phosphorylation site to autoinhibition was unknown. Using a combination of genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1 variants containing programmed phosphorylation to probe the interplay between Akt1 phosphorylation status and the auto-inhibitory function of the PH domain. Deletion of the PH domain increased the enzyme activity for all three phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of the PH domain relieved auto-inhibition by 295-fold. We next found that phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2 inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1 T308 and showed 4-fold decreased potency with Akt1 variants phosphorylated at Ser473. The data highlight the need to design more potent Akt1 inhibitors that are effective against the doubly phosphorylated and most pathogenic form of Akt1.

show abstract

miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway

Cited by 39 publications

References 28 publications

PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways

PTEN promotes apoptosis of H2O2‑injured rat nasal epithelial cells through PI3K/Akt and other pathways

MicroRNA Expression Profiling of Normal and Malignant Human Colonic Stem Cells Identifies miRNA92a as a Regulator of the LRIG1 Stem Cell Gene

Phosphorylation-Dependent Inhibition of Akt1

Contact Info

Product

Resources

About