Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: Plausible role in tumorigenesis

Sharma, Ujjawal; Pal, Devendra; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

doi:10.1016/j.biochi.2014.05.011

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…Cell viability was checked using MTT assay as described previously 37 . Briefly, in 96-well plates, 5000 cells/well were seeded and incubated overnight.…”

Section: Methodsmentioning

confidence: 99%

Reduction in H3K4me patterns due to aberrant expression of methyltransferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications

Kumar

Kumari

Sharma

et al. 2019

Sci Rep

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Renal cell carcinoma (RCC) is the leading cause among cancer-related deaths due to urological cancers, which results in response to combination of genetic and epigenetic factors. Histone methylations have been implicated in renal tumorigenesis but their clinical significance and underlying pathology are unexplored. Here, we elucidated the histone 3 lysine 4 (H3K4) methylation patterns in clear cell RCC and its underlying pathology. Lower cellular levels of H3K4 mono-methylation, -dimethylation and –tri-methylation were fraternized with higher TNM staging and Fuhrman grading as well as tumor metastasis. Further, the expression profile of 20 H3K4 modifiers revealed the significant over-expression of histone demethylases compared to methyltransferases, indicating their role in the reduction of H3K4 methylation levels. In view of above facts, the role of LSD2 and KDM5A demethylases in RCC pathogenesis were explored using respective siRNAs. The RCC cells exhibited reduced cell viability after knockdown of LSD2 and KDM5A genes with concomitant induction of apoptosis. In addition, propidium iodide staining demonstrated an arrest of RCC cells at S-phase and sub-G1 phase of the cell cycle. Taken together, these observations provide new pathological insights behind the alterations of H3K4 methylation patterns in ccRCC with their prognostic and therapeutic implications.

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“…Cell viability was checked using MTT assay as described previously 37 . Briefly, in 96-well plates, 5000 cells/well were seeded and incubated overnight.…”

Section: Methodsmentioning

confidence: 99%

Reduction in H3K4me patterns due to aberrant expression of methyltransferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications

Kumar

Kumari

Sharma

et al. 2019

Sci Rep

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“…Goat polyclonal IgG antibody directed against the human TRF1 (sc-1977, Santa Cruz, USA) or TRF2 (sc-9143, Santa Cruz, USA) was used to detect TRF1 and TRF2 in all the samples (92) of RCC, according to the method as already described in detail previously [ 18 ]. Briefly, 4 mm tissue sections were cut, dewaxed, and incubated in absolute methanol solution with 0.3 mL of hydrogen peroxide for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Over-Expression of Telomere Binding Factors (TRF1 & TRF2) in Renal Cell Carcinoma and Their Inhibition by Using SiRNA Induce Apoptosis, Reduce Cell Proliferation and Migration Invitro

et al. 2015

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Telomere binding factors viz. TRF1 and TRF2 are a part of sheltrin complex that are present exclusively at the ends of chromosomes. These factors play an important role in maintaining chromosomal integrity at the ends. However, their status and role are not clear in renal cell carcinoma (RCC). Therefore, the present study was conducted to evaluate TRF1 and TRF2 expressions in RCC tissues. Further, the role of these factors involved in tumorigenesis was elucidated by gene silencing using siRNA in RCC cell line (A498). The present study documented a significant over-expression of TRF1 (P = 0.005) and TRF2 (P = 0.0048) mRNAs by real time PCR in RCC tissues as compared with adjacent normal kidney tissues. Immunohistochemistry studies also revealed higher expression of TRF1 and TRF2 proteins in RCC. Moreover, TRF1 or TRF2 gene silencing using siRNA showed marked reduction in proliferation of RCC cells (P = 0.000). Further, significantly induced cell cycle arrest (P = 0.000) and apoptosis of RCC cells (P = 0.000) was documented upon TRF1 or TRF2 gene silencing. Henceforth, the results deduce that TRF1 or TRF2 inhibitions play an important role in the induction of apoptosis in A498 cells, which may serve as a potential therapeutic target in RCC.

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“…According to Sharma et al [ 68 ], decreased activity of TNSALP is remarkable in renal cell carcinoma (RCC). Forced expression of ALPL cDNA in renal cell carcinoma (RCC) cell lines resulted in decreased migratory property and cell viability compared with the controls.…”

Section: Various Biological Roles Of Tnsalpmentioning

confidence: 99%

Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm

Saitoh

Kiyokawa

Iwase

et al. 2021

Cells

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Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification. In humans, four forms of ALP cDNA have been cloned, among which tissue-nonspecific ALP (TNSALP) (TNSALP) is widely distributed in the liver, bone, and kidney, making it an important marker in clinical and basic research. Interestingly, TNSALP is highly expressed in juvenile cells, such as pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells (iPSCs)) and somatic stem cells (i.e., neuronal stem cells and bone marrow mesenchymal stem cells). Hypophosphatasia is a genetic disorder causing defects in bone and tooth development as well as neurogenesis. Mutations in the gene coding for TNSALP are thought to be responsible for the abnormalities, suggesting the essential role of TNSALP in these events. Moreover, a reverse-genetics-based study using mice revealed that TNSALP is important in bone and tooth development as well as neurogenesis. However, little is known about the role of TNSALP in the maintenance and differentiation of juvenile cells. Recently, it was reported that cells enriched with TNSALP are more easily reprogrammed into iPSCs than those with less TNSALP. Furthermore, in bone marrow stem cells, ALP could function as a “signal regulator” deciding the fate of these cells. In this review, we summarize the properties of ALP and the background of ALP gene analysis and its manipulation, with a special focus on the potential role of TNSALP in the generation (and possibly maintenance) of juvenile cells.

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Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: Plausible role in tumorigenesis

Cited by 10 publications

References 35 publications

Reduction in H3K4me patterns due to aberrant expression of methyltransferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications

Reduction in H3K4me patterns due to aberrant expression of methyltransferases and demethylases in renal cell carcinoma: prognostic and therapeutic implications

Over-Expression of Telomere Binding Factors (TRF1 & TRF2) in Renal Cell Carcinoma and Their Inhibition by Using SiRNA Induce Apoptosis, Reduce Cell Proliferation and Migration Invitro

Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm

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