NPRL2 gene expression in the progression of colon tumors

Yogurtcu, B.; Hatemı, İbrahim; Aydın, İbrahim; Buyru, Nur

doi:10.4238/2012.september.12.3

Cited by 8 publications

(10 citation statements)

References 22 publications

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“…Mutation of NPRL2 or DEPDC5, genes encoding GATOR1 components, has been linked to lung, breast, ovarian, kidney, liver and brain cancers [50,[107][108][109][110][111][112][113]. Indeed, cancer cells harboring homozygous loss of function mutations in GATOR1 components have elevated mTORC1 activity that is insensitive to amino acid starvation [50].…”

Section: Human Diseases Associated With Defects In Amino Acid Sensingmentioning

confidence: 99%

Multiple amino acid sensing inputs to mTORC1

2015

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The evolutionarily conserved target of rapamycin complex 1 (TORC1) is a master regulator of cell growth and metabolism. In mammals, growth factors and cellular energy stimulate mTORC1 activity through inhibition of the TSC complex (TSC1-TSC2-TBC1D7), a negative regulator of mTORC1. Amino acids signal to mTORC1 independently of the TSC complex. Here, we review recently identified regulators that link amino acid sufficiency to mTORC1 activity and how mutations affecting these regulators cause human disease.

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Section: Human Diseases Associated With Defects In Amino Acid Sensingmentioning

confidence: 99%

Multiple amino acid sensing inputs to mTORC1

2015

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“…The downregulation or silencing of the NPRL2 gene via aberrant splicing transcripts, multiple exon deletions or intragenic homozygous deletions, has been observed in renal cell carcinoma, lung cancer and other types of cancer and cancer-derived cell lines in humans, suggesting that NPRL2 may be a tumor suppressor, the inactivation of which may promote tumori-genesis ( 4 – 8 ). Decreased mRNA and protein expression levels of NPRL2 have also been found in CRC tissues, compared with matched normal tissues and adenomas ( 9 , 10 ). However, how the functional characterization of NPRL2 contributes to the progression of CRC remains to be elucidated.…”

Section: Introductionmentioning

confidence: 98%

Functional characterization of the nitrogen permease regulator-like-2 candidate tumor suppressor gene in colorectal cancer cell lines

Liu

Pei

et al. 2015

Molecular Medicine Reports

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The nitrogen permease regulator-like-2 (NPRL2) gene is a candidate tumor suppressor gene, which has been identified in the 3p21.3 human chromosome region. Decreased expression levels of NPRL2 have been observed in colorectal cancer (CRC) tissues, however, the function of NPRL2 in CRC progression remains to be fully elucidated. The present study investigated the biological characteristics of the HCT116 and HT29 CRC cell lines overexpressing exogenous NPRL2. NPRL2 recombinant lentiviral vectors were also constructed and transfected in the present study. Cell growth was determined using a Cell Counting Kit-8 assay and a colony formation assay. The cell cycle and rate of apoptosis were assessed using flow cytometric analysis. Transwell assays were used to evaluate cell invasion. The protein expression of phosphorylated (p)-AKT and caspase 3, B-cell lymphoma 2 (Bcl2) and Bcl-2-associated X protein apoptosis-associated genes, were detected using western blotting. The results revealed that NPRL2 overexpression inhibited cell growth, induced cell cycle G1 phase arrest, promoted apoptosis and inhibited invasion in the two human CRC cell lines. Furthermore, the protein expression levels of p-AKT and Bcl2 were significantly reduced in the NPRL2-transfected HCT116 and HT29 cells, compared with the mock-transfected group and control group, while the protein expression of caspase-3 was increased. Therefore, NPRL2 acted as a functional tumor suppressor in the CRC cell lines.

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“…This gene occupies 3.3 kb and contains 11 exons, coding for a main 1.8 kb mRNA and producing a protein of 380 amino-acid residues [16]. The NPRL2 is widely expressed in many normal human tissues, including the skeletal muscle, lung, cardiac, liver, kidney, and pancreas [16,18], but reduced expression of NPRL2 via microsatellite instability of the promoter region, multiple exon deletions, aberrant splicing transcripts, and homozygous deletions in the 3'end [18][19][20] has been described in a variety of human tumors, such as head and neck carcinoma, breast cancer, lung cancer, esophageal carcinoma, hepatocellular carcinoma, colorectal cancer, renal cancer, female genital tract cancer, and osteosarcoma [5,15,18,19,[21][22][23][24][25][26]. Meanwhile, NPRL2 suppresses tumor development both in vitro and in vivo [26][27][28][29], and regulates cell cycle checkpoint signaling, DNA mismatch repair and apoptosis [8,16,20].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of nitrogen permease regulator like‐2 activates PDK1‐AKT1 and contributes to the malignant growth of glioma cells

Huang

Cheng

et al. 2015

Molecular Carcinogenesis

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Nitrogen permease regulator like-2(NPRL2) is a candidate tumor suppressor gene(TSG) located on chromosome 3p21.3 and deletions frequently occur in this region, leading to canceration. Recently, molecular pathologic researches have provided valuable insights into the downregulation of NPRL2 in carcinogenesis in some types of cancers. However, very little is known about genetic changes of NPRL2 involved in glioma. Here, for the first time, we aimed to understand the expression levels, functions and mechanisms of NPRL2 for progression of glioma. We clearly demonstrated that NPRL2 expression was decreased in glioma and was negatively correlated with the histologic grade. The upregulation of NPRL2 expression in glioma cells inhibited proliferation by inducing G0/G1 cell cycle arrest in vitro and suppressed the growth of xenotransplanted tumors. In contrast, siRNA-mediated knockdown of NPRL2 promoted glioma growth. The anti-cancer effects of NPRL2 were involved in dephosphorylation of PDK1 and downstream AKT1 resulting in inactivation of the PDK1-AKT1 signaling pathway, this ultimately increased the expression of p21 and p27, and inactivated CDK2 and CDK4. Our data confirmed NPRL2 was downregulated in gliomas. More importantly, NPRL2 was able to inhibit cell proliferation in vitro and repress tumorigenicity in vivo, suggesting its role as a tumor suppressor. Our data provide a basis for the further development of a promising therapeutic target for glioma. © 2015 Wiley Periodicals, Inc.

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NPRL2 gene expression in the progression of colon tumors

Cited by 8 publications

References 22 publications

Multiple amino acid sensing inputs to mTORC1

Multiple amino acid sensing inputs to mTORC1

Functional characterization of the nitrogen permease regulator-like-2 candidate tumor suppressor gene in colorectal cancer cell lines

Downregulation of nitrogen permease regulator like‐2 activates PDK1‐AKT1 and contributes to the malignant growth of glioma cells

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