SLC25A28

Last update 08 May 2025

Basic Info

Synonyms

hMRS3/4, MFRN2, Mitochondrial iron transporter 2

+ [9]

Introduction

Mitochondrial iron transporter that mediates iron uptake. Probably required for heme synthesis of hemoproteins and Fe-S cluster assembly in non-erythroid cells.

100 Clinical Results associated with SLC25A28

100 Translational Medicine associated with SLC25A28

0 Patents (Medical) associated with SLC25A28

Literatures (Medical) associated with SLC25A28

15 Apr 2025·The FASEB Journal

Artesunate induces ferroptosis in osteosarcoma through NCOA4‐mediated ferritinophagy

Article

Author: Xu, Ruiqing ; Shi, Jiandang ; Wei, Daihao ; Huang, Rui ; Yang, Zongqiang ; Zheng, Jianping

AbstractOsteosarcoma (OS) is a prevalent primary malignant bone tumor that lacks effective therapeutic interventions. Artesunate (ART) has been proved to have remarkable treatment effects on severe malaria and anti‐tumor properties. This study aimed to investigate the anti‐OS effects and underlying mechanisms of ART. The potential mechanisms of ART‐mediated anti‐OS activity were analyzed by using RNA sequencing, iron accumulation, lipid peroxidation, western blotting, and small interfering RNA (siRNA) transfection. In vivo, a xenograft mice model was adopted to explore the anticancer effect of ART. The present study revealed that ART significantly suppressed OS cell proliferation. Subsequent results suggested that ART exerted anti‐OS activity mainly through the ferroptosis pathway. ART decreased the GSH/GSSG ratio, xCT and GPX4 expression, while increasing MDA and lipid peroxidation, which were reversed by Fer‐1, DFO, 3‐MA, and NCOA4 silencing. Mechanistically, ART upregulated the expression of TFR and DMT1, and triggered ferritinophagy by upregulating the expression of NCOA4, which increased Fe2+ accumulation and triggered ferroptosis. In addition, cytoplasmic iron further activated Mfrn2‐mediated transportation of cytoplasmic free iron into the mitochondria, resulting in mitochondrial iron overload, eventually leading to lipid peroxidation and ferroptosis. Furthermore, in an OS xenograft mouse model, administration of ART inhibited tumor growth by ferroptosis. Collectively, our findings indicated that ART has the potential anti‐OS capacity through NCOA4‐mediated ferritinophagy, which might shed light on the future of OS therapy.

01 Apr 2025·Journal of the American College of Surgeons

Multi-Institutional Analysis of Pancreaticoduodenectomy for Nonfamilial Periampullary Adenoma: A Novel Risk Score to Guide Shared Decision-Making

Article

Author: Merchant, Nipun ; Ahmad, Syed A ; Hester, Caitlin ; Eng, Nina ; Kasting, Christina ; Prela, Orjola ; Russell, Maria C ; Kooby, David A ; Sigler, Gregory ; Sok, Caitlin ; Shah, Mihir M ; Sarmiento, Juan M ; Maithel, Shishir K ; Datta, Jashodeep ; Zafar, Nabeel ; Hariri, Hussein ; Marra, Angelo ; Kim, Hong Jin ; Alseidi, Adnan ; Scoggins, Charles ; Mavani, Parit T ; Wilson, Gregory ; Carpizo, Darren ; Fields, Ryan ; Weber, Sharon ; LeCompte, Michael ; Foroutani, Laleh

BACKGROUND:Pancreaticoduodenectomy (PD) may occasionally be indicated for complete removal of periampullary (duodenal and ampullary) adenomas (PAs). As compared with malignant indications, PD for benign or premalignant disease is often associated with increased morbidity. Although the Spigelman classification assesses malignancy risk for familial adenomatous polyposis (FAP)-related duodenal adenomas, no malignancy risk score (MRS) exists for non-FAP-related PAs. We developed an MRS for non-FAP-related PAs undergoing PD to weigh the risk of malignancy and postoperative morbidity.STUDY DESIGN:We retrospectively analyzed patients with non-FAP-related PA who underwent PD at 8 institutions (2010 to 2022). Patient and lesion factors associated with final malignant pathology were identified using multivariable logistic regression to create MRS. Postoperative complications were assessed according to MRS.RESULTS:Of 127 patients, 59 (46.5%) had evidence of malignancy on final pathology. The odds of malignancy were higher in patients aged 65 years or older (odds ratio [OR] 3.2, p = 0.01), having bile duct 9 mm or more (OR 3.3, p = 0.009), having preoperative symptoms (OR 7.7, p = 0.002), and having high-grade dysplasia (OR 7.5, p < 0.001). A MRS was derived ranging from 0 to 6: age 65 years or older = 1, bile duct 9 mm or more = 1, symptomatic = 2, and high-grade dysplasia = 2. Patients were stratified into low-risk (MRS 1 to 2, n = 26), intermediate-risk (MRS 3 to 4, n = 59), and high-risk groups (MRS 5 to 6, n = 26), with malignancy rates increasing with MRS (10.3%, 44.1%, and 88.2%, p < 0.001). Patients in the no- or low-risk group (MRS 0 to 2) had higher odds of major postoperative complications compared with patients in the intermediate- or high-risk group (MRS 3 or higher, OR 2.9, p = 0.047).CONCLUSIONS:This novel MRS stratifies the risk of malignancy in non-FAP-related PAs managed with PD. This score can be used to counsel patients who may require PD for complete tumor removal about their risk of harboring malignancy and their risk of major postoperative complications.

01 Apr 2025·International Journal of Biological Macromolecules

Long non-coding RNA ZFAS1 promotes ferroptosis by regulating the miR-185-5p/SLC25A28 axis in clear cell renal cell carcinoma

Article

Author: Jin, Hui ; Li, Yeping ; Li, Xinmiao ; Zhang, Minghong ; Tao, Qiqi ; Zhang, Weizhi ; Zheng, Jianjian ; Li, Yifei

Ferroptosis is a novel, iron-dependent regulated cell death mode. The biochemical features of ferroptosis include iron accumulation, lipid peroxidation, inhibition of glutathione peroxidase 4 (GPX4) and antioxidant glutathione (GSH) decrease through inhibition of the system xc^- transporter. Zinc finger NFX1 type-containing 1 (ZNFX1) antisense RNA 1 (ZFAS1) is a long non-coding RNA that has been identified as an oncogene in various types of cancers. However, its regulatory role and molecular mechanisms in clear cell renal cell carcinoma (ccRCC) ferroptosis remain unclear. In this study, the ferroptosis inducers (FINS) (erastin and RSL3) were found to increase ZFAS1 expression through the facilitation of SP1 binding to the ZFAS1 promoter. ZFAS1 increased mRNA and protein levels of solute carrier family 25 member 28 (SLC25A28) via functioning as a miR-185-5p sponge. Overexpressed SLC25A28 increased the production of ROS and caused a decrease in NADPH and GSH in cells treated with FINS. In addition, overexpression of ZFAS1 enhanced ferroptosis both in vitro and in vivo. Altogether, this study demonstrates that ZFAS1 is a crucial element of ferroptosis in ccRCC, as it is responsible for the regulation of miR-185-5p and SLC25A28. Introducing ferroptosis could be a beneficial approach to treat ccRCC patients with high ZFAS1 levels.

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SLC25A28

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