PRKAR2B plays an oncogenic role in the castration-resistant prostate cancer

Sha, Jianjun; Xue, Wei; Dong, Baijun; Pan, Jiahua; Wu, Xiaorong; Liu, Dong; Liu, Dongming; Huang, Yiran

doi:10.18632/oncotarget.14044

Cited by 22 publications

(32 citation statements)

References 34 publications

(40 reference statements)

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“…Results shown are the mean of two independent experiments AE SD (100 cells/experiment, *P < 0.5, **P < 0.01, ***P < 0.001, ns: not significant t-test). proteins Ran1Gap2 and Prkar2B were perturbed in the global proteome ( Fig 8B-D) [34,[58][59][60]. Consistent with the proteomics data, a significant increase in the cellular abundance of Cep131 and a significant decrease in SLAIN2 was detected using immunoblotting experiments ( Fig 4G).…”

Section: Loss Of Satellites Leads To a Rearrangement Of The Global Prsupporting

confidence: 83%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action remain poorly understood. Here, we generated a kidney epithelial cell line ( IMCD 3) lacking satellites by CRISPR /Cas9‐mediated PCM 1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full‐length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three‐dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.

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Section: Loss Of Satellites Leads To a Rearrangement Of The Global Prsupporting

confidence: 83%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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“…Protein kinase cAMP‐dependent regulatory type II beta (PRKAR2B) plays a role in oocyte maturation, 8 regulates murine and human adipocyte differentiation 9 and inhibits the effect of cAMP responsive element binding protein (CREB) activity in T cells 10 . Recently, we identified PRKAR2B as a novel oncogene implicated in the development of CRPC 11,12 . Moreover, PRKAR2B induces the epithelial‐mesenchymal transition process and promotes prostate cancer metastasis by activating Wnt/β‐catenin signalling pathway 13 …”

Section: Introductionmentioning

confidence: 99%

PRKAR2B‐HIF‐1α loop promotes aerobic glycolysis and tumour growth in prostate cancer

et al. 2020

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Objectives Reprogramming of cellular metabolism is profoundly implicated in tumorigenesis and can be exploited to cancer treatment. Cancer cells are known for their propensity to use glucose‐dependent glycolytic pathway instead of mitochondrial oxidative phosphorylation for energy generation even in the presence of oxygen, a phenomenon known as Warburg effect. The type II beta regulatory subunit of protein kinase A (PKA), PRKAR2B, is highly expressed in castration‐resistant prostate cancer (CRPC) and contributes to tumour growth and metastasis. However, whether PRKAR2B regulates glucose metabolism in prostate cancer remains largely unknown. Materials and methods Loss‐of‐function and gain‐of‐function studies were used to investigate the regulatory role of PRKAR2B in aerobic glycolysis. Real‐time qPCR, Western blotting, luciferase reporter assay and chromatin immunoprecipitation were employed to determine the underlying mechanisms. Results PRKAR2B was sufficient to enhance the Warburg effect as demonstrated by glucose consumption, lactate production and extracellular acidification rate. Mechanistically, loss‐of‐function and gain‐of‐function studies showed that PRKAR2B was critically involved in the tumour growth of prostate cancer. PRKAR2B was able to increase the expression level of hypoxia‐inducible factor 1α (HIF‐1α), which is a key mediator of the Warburg effect. Moreover, we uncovered that HIF‐1α is a key transcription factor responsible for inducing PRKAR2B expression in prostate cancer. Importantly, inhibition of glycolysis by the glycolytic inhibitor 2‐deoxy‐d‐glucose (2‐DG) or replacement of glucose in the culture medium with galactose (which has a much lower rate than glucose entry into glycolysis) largely compromised PRKAR2B‐mediated tumour‐promoting effect. Similar phenomenon was noticed by genetic silencing of HIF‐1α. Conclusions Our study identified that PRKAR2B‐HIF‐1α loop enhances the Warburg effect to enable growth advantage in prostate cancer.

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“…Included in the PKA family is cAMP-dependent type 2 regulatory subunit beta ( Prkar2b ), a form of RIIβ; these genes are primarily expressed in brain tissue, brown adipose tissue, and white adipose tissue [7, 8]. Prkar2b has the ability to regulate leukemia cell differentiation [9], plays a role in motoneurons [10] and alternative signaling of cAMP pathways [11], suppresses the effect of cAMP responsive element binding protein (CREB) activity in T cells [12], regulates adipocyte differentiation [13], and plays an oncogenic role in prostate cancer [14]. A recent study found that Prkar2b -deficient mice experience a decrease in white adipose tissue and an increase in resting metabolic activity, body temperature, and lipid hydrolysis [7].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of PRKAR2B Results in the Failure of Oocyte Maturation

Yoon¹,

Jang²,

Kim³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cyclic adenosine monophosphate (cAMP)-dependent type 2 regulatory subunit beta (Prkar2b) is a regulatory isoform of cAMP-dependent protein kinase (PKA), which is the primary target for cAMP actions. In oocytes, PKA and the pentose phosphate pathway (PPP) have important roles during the germinal vesicle (GV) stage arrest of development. Although the roles of the PKA signal pathway have been studied in the development of oocyte, there has been no report on the function of PRKAR2B, a key regulator of PKA. Methods: Using reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR (qRT-PCR), immunohistochemistry, and immunofluorescence, we determined the relative expression of Prkar2b in various tissues, including ovarian follicles, during oocyte maturation. Prkar2b-interfering RNA (RNAi) microinjection was conducted to confirm the effect of Prkar2b knockdown, and immunofluorescence, qRT-PCR, and time-lapse video microscopy were used to analyze Prkar2b-deficient oocytes. Results: Prkar2b is strongly expressed in the ovarian tissues, particularly in the growing follicle. During oocyte maturation, the highest expression of Prkar2b was during metaphase I (MI), with a significant decrease at metaphase II (MII). RNAi-mediated Prkar2b suppression resulted in MI-stage arrest during oocyte development, and these oocytes exhibited abnormal spindle formation and chromosome aggregation. Expression of other members of the PKA family (except for Prkaca) were decreased, and the majority of the PPP factors were also reduced in Prkar2b-deficient oocytes. Conclusion: These results suggest that Prkar2b is closely involved in the maturation of oocytes by controlling spindle formation and PPP-mediated metabolism.

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PRKAR2B plays an oncogenic role in the castration-resistant prostate cancer

Cited by 22 publications

References 34 publications

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

PRKAR2B‐HIF‐1α loop promotes aerobic glycolysis and tumour growth in prostate cancer

Knockdown of PRKAR2B Results in the Failure of Oocyte Maturation

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