INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival

Rynkiewicz, Natalie K.; Fedele, Clare G.; Chiam, Karen; Gupta, Ruta; Kench, James G.; Ooms, Lisa M; McLean, Catriona; Giles, Graham G.; Horvath, Lisa G.; Mitchell, Christina A.

doi:10.1002/pros.22895

Cited by 26 publications

(19 citation statements)

References 38 publications

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“…Many of 5-phosphatases hydrolyse PtdIns(3,4,5)P 3 to form PtdIns(3,4)P 2 , which is then further dephosphorylated by the inositol polyphosphate 4-phosphatases (4-phosphatases, INPP4A and INPP4B) to produce PtdIns(3)P ( Figure 1) [3]. INPP4B has recently been identified as a putative tumour suppressor in breast, prostate and thyroid cancer [43][44][45][46][47][48].…”

Section: Termination Of Pi3k/akt Signalling By the 5-phosphatasesmentioning

confidence: 99%

Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases

Eramo

Mitchell

2016

Biochemical Society Transactions

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The phosphoinositide 3-kinase (PI3K) generated lipid signals, PtdIns(3,4,5)P3 and PtdIns(3,4)P2, are both required for the maximal activation of the serine/threonine kinase proto-oncogene Akt. The inositol polyphosphate 5-phosphatases (5-phosphatases) hydrolyse the 5-position phosphate from the inositol head group of PtdIns(3,4,5)P3 to yield PtdIns(3,4)P2. Extensive work has revealed several 5-phosphatases inhibit PI3K-driven Akt signalling, by decreasing PtdIns(3,4,5)P3 despite increasing cellular levels of PtdIns(3,4)P2. The roles that 5-phosphatases play in suppressing cell proliferation and transformation are slow to emerge; however, the 5-phosphatase PIPP [proline-rich inositol polyphosphate 5-phosphatase; inositol polyphosphate 5-phosphatase (INPP5J)] has recently been identified as a putative tumour suppressor in melanoma and breast cancer and SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] inhibits haematopoietic cell proliferation. INPP5E regulates cilia stability and INPP5E mutations have been implicated ciliopathy syndromes. This review will examine 5-phosphatase regulation of PI3K/Akt signalling, focussing on the role PtdIns(3,4,5)P3 5-phosphatases play in developmental diseases and cancer.

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Section: Termination Of Pi3k/akt Signalling By the 5-phosphatasesmentioning

confidence: 99%

Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases

Eramo

Mitchell

2016

Biochemical Society Transactions

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“…Moreover, miR-590-3p mimics significantly downregulated, while miR-590-3p inhibitor remarkably upregulated the protein expression of INPP4B in both LNCaP and C4-2 cells (Figure 3(e)). As INPP4B acts as a tumor suppressor in PCa and its loss of expression is associated with poor prognosis for PCa patients, 7 we investigated the effects of miR-590-3p-mediated downregulation of INPP4B on cell proliferation and invasion in PCa cells. INPP4B was overexpressed by using pcDNA3.1(+)/INPP4B (Figure 3(f)), and as a result, miR-590-3p mimic-induced cell proliferation and invasion were significantly abrogated in both LNCaP and C4-2 cells (Figure 3(g) and (h)).…”

Section: Inpp4b Is a Direct Target Of Mir-590-3pmentioning

confidence: 99%

MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells

Chen

Luo

2017

Tumour Biol.

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Inositol polyphosphate 4-phosphatase type II emerges as a tumor suppressor in prostate cancer, and its loss of expression is associated with poor prognosis for prostate cancer. However, the mechanism of downregulation of inositol polyphosphate 4-phosphatase type II in prostate cancer development has not yet been fully clarified. In this study, microRNA-590-3p was found to be upregulated in both prostate cancer tissues and cell lines. Overexpression of microRNA-590-3p by microRNA-590-3p mimics promoted prostate cancer cell proliferation and invasion and accelerated the growth of xenografted tumors, while microRNA-590-3p inhibitors contributed to inhibition of cellular proliferation and invasion as well as tumor growth. A dual-luciferase reporter assay and expression analysis further confirmed that inositol polyphosphate 4-phosphatase type II was a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p led to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II could reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells. Taken together, our findings reveal that microRNA-590-3p is a potential onco-microRNA that participates in carcinogenesis of human prostate cancer by suppressing inositol polyphosphate 4-phosphatase type II expression and involving the Akt/FoxO3a pathway. MicroRNA-590-3p may represent a potential therapeutic target for prostate cancer patients.

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“…INPP4B was initially characterized as an inositol polyphosphate phosphatase hydrolyzing PtdIns (3,4)P2 to PtdIns(3)P. As the intracellular PI (3,4)P2 is required for the full activation of Akt, a critical oncogene in various cancers, INPP4B can restrain the PI3K/Akt signaling (5). Recently, INPP4B was shown to play a tumor suppressor role in variety of cancers, including lung, prostate, bladder and melanocytic cancers (6)(7)(8)(9). The tumor suppressive mechanism of INPP4B has been attributed to its negative regulation role in PI3K/Akt signaling.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-605 functions as a tumor suppressor by targeting INPP4B in melanoma

et al. 2017

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MicroRNAs (miRNAs) play crucial roles in the initiation and progression of various cancers, including melanoma. Recently, the genetic variants and deregulation of miR-605 have been reported to participate in carcinogenesis. However, the expression status of the miR-605 in melanoma tissues and its role in melanoma progression remain unknown. In this study, we found that miR-605 was significantly downregulated in melanoma cell lines and clinical specimens. Further function studies demonstrated that miR-605 suppressed melanoma cell growth both in vitro and in vivo. Moreover, INPP4B gene was identified as a target of miR-605 through bioinformatics analysis and luciferase reporter assays. Further analysis demonstrated that the inhibition of INPP4B mediated SGK3 activation was required for the suppressive role of miR-605 on melanomas cell growth. Collectively, our data suggest that miR-605 functions as a tumor suppressor by negatively regulating INPP4B mediated SGK3 activation in melanoma and may present a potential target for therapeutic intervention.

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INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival

Cited by 26 publications

References 38 publications

Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases

Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5-phosphatases

MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells

MicroRNA-605 functions as a tumor suppressor by targeting INPP4B in melanoma

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