Post-transcriptional regulation of the human reduced folate carrier as a novel adaptive mechanism in response to folate excess or deficiency

Hou, Zhanjun; Orr, Steve; Matherly, Larry H.

doi:10.1042/bsr20140065

Cited by 10 publications

(10 citation statements)

References 33 publications

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“…Expression of RFC has demonstrated improved response to leucovorin (79). RFC acts like a transcellular ferry by which folates are delivered into cells from the systemic circulation, and RFC-mediated transport of folinic acid (leucovorin) has been well described (80).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

et al. 2017

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There has been an alarming rise in the incidence of esophageal adenocarcinoma which continues to have poor survival rates primarily due to lack of effective chemotherapy and presentation at advanced stages. Over a dozen chemotherapeutic agents are FDA approved for esophageal cancer (EC), and a two or three-drug combination is typically prescribed as first-line therapy for the majority of EC patients, administered either pre or post-operatively with esophageal resection. We have noticed significant variability in adjuvant and neoadjuvant regimens used in the community setting. The aim of this study was to review the various drug regimens used in the neoadjuvant setting for EC patients with adenocarcinoma undergoing resection at a single tertiary referral center in the Midwest. A total of 123 patients (stage II–III) underwent esophageal resection after neoadjuvant treatment at the center. Overall, 18 distinct drug regimens were used in 123 patients including two patients who received targeted therapy. Median survival post-surgery for this group was 11.2 months with no single regimen offering a survival advantage. These results reveal an unclear algorithm of how accepted regimens are prescribed in the community setting as well as a dire need for agents that are more effective. Additionally, it was noted that although proteomic markers have been found to predict drug response to 92% of the FDA-approved drugs in EC (12 of 13), according to pathology reports, molecular diagnostic testing was not used to direct treatment in this cohort. We therefore propose potential strategies to improve clinical outcomes including the use of a robust molecular oncology diagnostic panel and discuss the potential role for targeted chemotherapy and/or immunotherapy in the management of EC patients.

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

et al. 2017

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“…Hou et al, (2014), using cultured HeLa cells showed that RFC undergoes posttranscriptional regulation in response to folate excess or deficiency [35]. To our knowledge, our results have shown for the first time that folate concentration in serum cord blood of newborns may be related to the expression of FOLR1 in human placentas.…”

Section: Discussionsupporting

confidence: 50%

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

et al. 2017

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Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32–36 weeks, n = 51). Term placentas were used as controls (T, 37–41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

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“…As far as mRNA stability of folate transporters is concerned, no change in mRNA half life of PCFT, RFC, and FR was observed on ethanol exposure; however, FD treatment resulted in decrease in half life of PCFT and RFC from 4.9 to 3 h and from 2.6 to 1.6 h, respectively, without affecting FR. Similar study conducted on HeLa cells has reported a significant reduction in turnover of hRFC transcripts on decreasing concentration of 5-formyl tetrahydrofolate (leucovorin) [46]. This seems to be some kind of homeostatic mechanism in order to control the expression of folate transporters in conditions of FD, and it is also transporter specific.…”

Section: Discussionmentioning

confidence: 82%

Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency

Thakur

Rahat

et al. 2015

Mol Cell Biochem

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Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in conditions of FD and ethanol exposure in human embryonic kidney cell line. Also, the reversible nature of effects mediated by ethanol exposure and FD was determined by folate repletion and ethanol removal. For ethanol treatment, HEK293 cells were grown in medium containing 100 mM ethanol, and after treatment, one group of cells was shifted on medium that was free from ethanol. For FD treatment, cells were grown in folate-deficient medium followed by shifting of one group of cells on folate containing medium. FD as well as ethanol exposure resulted in an increase in folate uptake which was due to an increase in expression of folate transporters, i.e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level. The effects mediated by ethanol exposure and FD were reversible on removal of treatment. Promoter region methylation of folate transporters remained unaffected after FD and ethanol exposure. As far as transcription rate of folate transporters is concerned, an increase in rate of synthesis was observed in both ethanol exposure and FD conditions. Additionally, mRNA life of folate transporters was observed to be reduced by FD. An increased expression of folate transporters under ethanol exposure and FD conditions can be attributed to enhanced rate of synthesis of folate transporters.

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Post-transcriptional regulation of the human reduced folate carrier as a novel adaptive mechanism in response to folate excess or deficiency

Cited by 10 publications

References 33 publications

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

RETRACTED: Neoadjuvant Therapy for Esophageal Adenocarcinoma in the Community Setting—Practice and Outcomes

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

Increased synthesis of folate transporters regulates folate transport in conditions of ethanol exposure and folate deficiency

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