The Akt pathway in oncology therapy and beyond (Review)

Niţulescu, George Mihai; Venter, Maryna van de; Nițulescu, Georgiana; Ungurianu, Anca; Juzenas, Petras; Peng, Qian; Olaru, Octavian Tudorel; Grădinaru, Daniela; Tsatsakis, Aristidis; Tsoukalas, Dimitris; Spandidos, Demetrios A.; Margină, Denisa

doi:10.3892/ijo.2018.4597

Cited by 215 publications

(218 citation statements)

References 173 publications

(197 reference statements)

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“…The Cox regression analysis was carried out for the calculation of the miR-298 prognostic score in CRC ( (Nitulescu et al, 2018;Pópulo, Lopes, & Soares, 2012). Moreover, as a lipid phosphatase, PTEN is shown to have a distinctive role in both innate and adaptive immunity (Chen & Guo, 2017;Li et al, 2016).…”

Section: Prognostic Value Of Mir-298 Elevation In Crc Patientsmentioning

confidence: 99%

miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

Arabsorkhi

Gharib

Khojini

et al. 2019

Journal Cellular Physiology

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Evidence indicate that the miR-298 dysregulation might associate with colorectal cancer (CRC) development. Herein, we evaluated the effect of miR-298 dysregulation on colon cancer invasiveness. First, metabolic activity, cell cycle progression, apoptosis, and invasion of miR-298 overexpressed/knocked out colon cancer cells were examined and combined with their transcriptome analysis data for better visualization of miR-298 intracellular signaling networks. Interaction between miR-298 and its target was evaluated with luciferase assay and validated using western blot analysis. The proportion of abnormal miR-298 level was investigated in tumor samples, matched normal adjacent tissues, and plasmas of 100 CRC patients, and also compared with 100 normal plasma samples. TheMann-Whitney U test was performed to assess miR-298 differences among the studied groups, and the correlation between miR-298 and the risk of CRC was shown by univariate and multivariate logistic regression. The data indicate that miR-298 overexpression promoted proliferation and metastasis in CRC cells via targeting phosphatase and tensin homolog. Comparative analysis of CRC tumors, normal adjacent tissues, and plasmas indicated a significant miR-298 upregulation in tumors and plasmas (1.72-fold and 1.65fold, respectively; p < .001). Also, the aberrant level of miR-298 contributed with CRC tumor differentiation, TNM stage and lymph node metastasis (p < .001), and independently associated with poor survival of CRC patients (p < .029; hazard ratio: 1.292; 95% confidence interval: 0.339-2.184). Collectively, these data showed that abnormal level of miR-298 correlated with cancer development and through that lowered the overall survival rate of CRC patients. Therefore, miR-298 could be considered as a therapeutic target for CRC. K E Y W O R D S colorectal cancer, invasion, metastasis, microRNA-298, PTEN

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Section: Prognostic Value Of Mir-298 Elevation In Crc Patientsmentioning

confidence: 99%

miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

Arabsorkhi

Gharib

Khojini

et al. 2019

Journal Cellular Physiology

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“…AMPK is expressed ubiquitously and is involved in cell growth, metabolism and transcription, and plays a key role in the regulation of cellular and whole-body energy homeostasis [36][37][38]. The outputs of AKT signaling have been well reviewed [17,[39][40][41].…”

Section: Introductionmentioning

confidence: 99%

In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds

et al. 2020

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The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) activates CAMK1, CAMK4, AMPK, and AKT, leading to numerous physiological responses. The deregulation of CAMKK2 is linked to several diseases, suggesting the utility of CAMKK2 inhibitors for oncological, metabolic and inflammatory indications. In this work, we demonstrate that STO-609, frequently described as a selective inhibitor for CAMKK2, potently inhibits a significant number of other kinases. Through an analysis of literature and public databases, we have identified other potent CAMKK2 inhibitors and verified their activities in differential scanning fluorimetry and enzyme inhibition assays. These inhibitors are potential starting points for the development of selective CAMKK2 inhibitors and will lead to tools that delineate the roles of this kinase in disease biology.

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“…It is well known that oncogenic AKT kinase is a key regulator of cell growth, cell‐cycle progression, apoptosis etc . The knockdown and overexpression of PGK1 can inhibit and enhance AKT phosphorylation, respectively.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

Chen

Zhuang

Wang

et al. 2019

J of Cellular Biochemistry

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Dysregulation of microRNAs frequently contributes to the occurrence and progression of human diseases, including hepatocellular carcinoma (HCC). In this study, the role of miR‐450b‐3p in HCC was investigated. Gene Expression Omnibus database and HCC specimens were used to evaluate the expression level of miR‐450b‐3p and the patient's prognosis. Cell functional analyses and tumor xenograft model were used to assess the role of miR‐450b‐3p in HCC. Bioinformatics was used to predict the downstream target gene of miR‐450b‐3p, which was verified by dual‐luciferase reporter assay. MiR‐450b‐3p was found to be downregulated in HCC cell lines and tissues, compared with nontransformed immortal hepatic cells and adjacent normal liver tissues, respectively. Lower expression of miR‐450b‐3p was associated with poor overall survival and disease‐free survival in patients with HCC. Ectopic expression of miR‐450b‐3p inhibited HCC cell viability, colony formation, and cell‐cycle progression in vitro, and suppressed the growth of HCC xenograft tumors in vivo. Interestingly, a negative correlation between miR‐450b‐3p and phosphoglycerate kinase 1 (PGK1) protein was observed among HCC specimens. Additionally, miR‐450b‐3p inhibited PGK1 expression and phosphorylation of protein kinase B in HCC cell lines. Further experiments confirmed that PGK1 was a direct target of miR‐450b‐3p. Moreover, restoration of PGK1 abrogated the inhibitory effect of miR‐450b‐3p on HCC proliferation and cell division. In conclusion, miR‐450b‐3p is downregulated in human HCC and exerts tumor suppressive effects at least in part by inhibiting PGK1.

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The Akt pathway in oncology therapy and beyond (Review)

Cited by 215 publications

References 173 publications

miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

miR‐298 plays a pivotal role in colon cancer invasiveness by targeting PTEN

In Depth Analysis of Kinase Cross Screening Data to Identify CAMKK2 Inhibitory Scaffolds

MicroRNA‐450b‐3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma

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