Knockdown of the Sodium-Dependent Phosphate Co-Transporter 2b (NPT2b) Suppresses Lung Tumorigenesis

Hong, Sun; Minai-Tehrani, Arash; Chang, Simyung; Jiang, Hu‐Lin; Lee, Somin; Lee, Ah‐Young; Seo, Hwi Won; Chae, Chanhee; Beck, George R.; Cho, Myung‐Haing

doi:10.1371/journal.pone.0077121

Cited by 40 publications

(29 citation statements)

References 31 publications

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“…30,31 In gastric cancer cells, miR-15b promotes cell growth and metastasis both in vitro and in vivo. 32 In addition, it could regulate endothelial differentiation of breast cancer stem-like cells.…”

Section: Discussionmentioning

confidence: 99%

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

et al. 2015

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MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. We detected miR-15b expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-15b on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-15b level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens. miR-15b was significantly upregulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-15b regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified phosphatidylethanolamine-binding protein 4 (PEBP4) as a direct and functional target of miR-15b. Small-interfering RNA-mediated PEBP4 knockdown revealed similar effects as that of ectopic miR-15b expression, whereas overexpression of PEBP4 attenuated the function of miR-15b in lung adenocarcinoma cells. Increased miR-15b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of PEBP4, decreased sensitivity to cisplatin and poor prognosis. Our results suggest that upregulation of miR-15b could suppress PEBP4 expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.

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Section: Discussionmentioning

confidence: 99%

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

et al. 2015

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“…4). Consequently, the Na/Pi co-transporter NPT2b is abnormally expressed in various cancers, and targeting phosphate transporter is effective for lung cancer therapy (Hong et al, 2013).…”

Section: Relationship Of the Na/pi Co-transporter Npt2b With Cancermentioning

confidence: 99%

“…More research and analyses are required to determine the appropriate amount of phosphorus intake based on age, gender, and the presence of any disease. Furthermore, targeting genes encoding phosphate transporters represent a novel avenue (Hong et al, 2013) with permission.…”

Section: Relationship Of the Na/pi Co-transporter Npt2b With Cancermentioning

confidence: 99%

Biological effects of inorganic phosphate: potential signal of toxicity

et al. 2015

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-Inorganic phosphate (Pi) plays crucial roles in several biological processes and signaling pathways. Pi uptake is regulated by sodium-dependent phosphate (Na/Pi) transporters (NPTs). Moreover, Pi is used as a food additive in food items such as sausages, crackers, dairy products, and beverages. However, the high serum concentration of phosphate (> 5.5 mg/dL) can cause adverse renal effects, cardiovascular effects including vascular or valvular calcification, and stimulate bone resorption. In addition, Pi can also alter vital cellular signaling, related to cell growth and cap-dependent protein translation. Moreover, intake of dietary Pi, whether high (1.0%) or low (0.1%), affects organs in developing mice, and is related to tumorigenesis in mice. The recommended dietary allowance (RDA) of Pi is the daily dietary intake required to maintain levels above the lower limit of the range of normal serum Pi concentration (2.7 mg/dL) for most individuals (97-98%). Thus, adequate intake of Pi (RDA; 700 mg/day) and maintenance of normal Pi concentration (2.7-4.5 mg/dL) are important for health and prevention of diseases caused by inadequate Pi intake.

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“…Applications of RNAi-based experiments to in vivo cancer targeting and therapy experiments using synthetic siRNAs also have been proven as effective methods [12][13][14]. Various in vivo experiments using cationic carriers with DNA have been performed for cancer gene therapy [15].…”

Section: Introductionmentioning

confidence: 99%

“…When complexes of GPT-SPE with siOPN were delivered to tumor-bearing nude mice, tumor growth and proliferation were significantly suppressed in GPT-SPE with siOPN-treated group compared with non-treated group [13]. Moreover, repeated aerosol delivery of siRNA targeting the sodium-dependent phosphate co-transporter 2b (NPT-2b) with GPT-SPE inhibited lung cancer in K-ras LA1 lung cancer model mice through induction of apoptosis [14].…”

Section: Introductionmentioning

confidence: 99%

Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA

Cho

Hong

Singh

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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Knockdown of the Sodium-Dependent Phosphate Co-Transporter 2b (NPT2b) Suppresses Lung Tumorigenesis

Cited by 40 publications

References 31 publications

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

Biological effects of inorganic phosphate: potential signal of toxicity

Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA

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