General Information of the Ferroptosis Regulator (ID: REG10442)
Regulator Name Poly(rC)-binding protein 2 (PCBP2)
Synonyms
Alpha-CP2; Heterogeneous nuclear ribonucleoprotein E2
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Gene Name PCBP2
Gene ID 5094
Regulator Type Protein coding
Uniprot ID Q15366
Sequence
MDTGVIEGGLNVTLTIRLLMHGKEVGSIIGKKGESVKKMREESGARINISEGNCPERIIT
LAGPTNAIFKAFAMIIDKLEEDISSSMTNSTAASRPPVTLRLVVPASQCGSLIGKGGCKI
KEIRESTGAQVQVAGDMLPNSTERAITIAGIPQSIIECVKQICVVMLETLSQSPPKGVTI
PYRPKPSSSPVIFAGGQDRYSTGSDSASFPHTTPSMCLNPDLEGPPLEAYTIQGQYAIPQ
PDLTKLHQLAMQQSHFPMTHGNTGFSGIESSSPEVKGYWGLDASAQTTSHELTIPNDLIG
CIIGRQGAKINEIRQMSGAQIKIANPVEGSTDRQVTITGSAASISLAQYLINVRLSSETG
GMGSS

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Function
Single-stranded nucleic acid binding protein that binds preferentially to oligo dC. Major cellular poly(rC)-binding protein. Binds also poly(rU). Acts as a negative regulator of antiviral signaling. Negatively regulates cellular antiviral responses mediated by MAVS signaling. It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation. Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid- like droplets in which CGAS is activated. Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity).; (Microbial infection) In case of infection by poliovirus, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation. Also plays a role in initiation of viral RNA replication in concert with the viral protein 3CD.

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HGNC ID
HGNC:8648
KEGG ID hsa:5094
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PCBP2 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Lung cancer ICD-11: 2C25
Responsed Drug Borneol Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
H460/CisR cells Lung large cell carcinoma Homo sapiens CVCL_C5S1
In Vivo Model
Male Balb/c nude mice (4-week-old) were purchased from SPF (Beijing) biotechnology co., LTD and maintained in the Experimental Animal Research Center of Chengdu University of TCM. After 1 week of adaptable feeding, H460/CDDP cells (5 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank to establish tumor model. When the tumor volume grows to 100 mm3, the tumor-bearing mice were randomly divided into the following four treatment groups: a control group (Con, n = 6): intraperitoneal injection of saline once a day; vehicle group (Vehicle, n = 6): intragastric administration of 2% tween and intraperitoneal injection of saline; d-borneol low-dose group (Bor-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day; d-borneol high-dose group (Bor-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day; CDDP group (CDDP, n = 6): intraperitoneal injection of cisplatin (3 mg/kg) every two days; a low-dose combination treatment group (C+B-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days; a high-dose combination treatment group (C+B-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days. We usually first orally gavage d-borneol, and then inject cisplatin intraperitoneally half an hour later. After 14 days treatment, the samples were obtained from the mice for the further experiments.

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Response regulation d-borneol in combination with cisplatin induced ferroptosisviaNCOA4-mediated ferritinophagy and also increased the expression levels of ACSL4, regulated PCBP2 and PRNP to promote the conversion of Fe3+to Fe2+, reduced the activity or expression of antioxidants enzymes (GSH and HO-1), and induced ROS accumulation and thereby promoted ferroptosis. In addition, activation of autophagy inhibited progression of the EMT and increased sensitivity to cisplatin in cisplatin-resistant lung cancer cells.
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Poly(rC)-binding protein 2 (PCBP2) Protein coding
Responsed Drug Borneol Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
H460/CisR cells Lung large cell carcinoma Homo sapiens CVCL_C5S1
In Vivo Model
Male Balb/c nude mice (4-week-old) were purchased from SPF (Beijing) biotechnology co., LTD and maintained in the Experimental Animal Research Center of Chengdu University of TCM. After 1 week of adaptable feeding, H460/CDDP cells (5 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank to establish tumor model. When the tumor volume grows to 100 mm3, the tumor-bearing mice were randomly divided into the following four treatment groups: a control group (Con, n = 6): intraperitoneal injection of saline once a day; vehicle group (Vehicle, n = 6): intragastric administration of 2% tween and intraperitoneal injection of saline; d-borneol low-dose group (Bor-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day; d-borneol high-dose group (Bor-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day; CDDP group (CDDP, n = 6): intraperitoneal injection of cisplatin (3 mg/kg) every two days; a low-dose combination treatment group (C+B-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days; a high-dose combination treatment group (C+B-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days. We usually first orally gavage d-borneol, and then inject cisplatin intraperitoneally half an hour later. After 14 days treatment, the samples were obtained from the mice for the further experiments.

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Response regulation d-borneol in combination with cisplatin induced ferroptosisviaNCOA4-mediated ferritinophagy and also increased the expression levels of ACSL4, regulated PCBP2 and PRNP to promote the conversion of Fe3+to Fe2+, reduced the activity or expression of antioxidants enzymes (GSH and HO-1), and induced ROS accumulation and thereby promoted ferroptosis. In addition, activation of autophagy inhibited progression of the EMT and increased sensitivity to cisplatin in cisplatin-resistant lung cancer cells.
Borneol [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Lung cancer ICD-11: 2C25
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell adhesion molecules hsa04514
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
H460/CisR cells Lung large cell carcinoma Homo sapiens CVCL_C5S1
In Vivo Model
Male Balb/c nude mice (4-week-old) were purchased from SPF (Beijing) biotechnology co., LTD and maintained in the Experimental Animal Research Center of Chengdu University of TCM. After 1 week of adaptable feeding, H460/CDDP cells (5 x 106 cells in 0.1 ml phosphate-buffered saline) were subcutaneously injected into the right dorsal flank to establish tumor model. When the tumor volume grows to 100 mm3, the tumor-bearing mice were randomly divided into the following four treatment groups: a control group (Con, n = 6): intraperitoneal injection of saline once a day; vehicle group (Vehicle, n = 6): intragastric administration of 2% tween and intraperitoneal injection of saline; d-borneol low-dose group (Bor-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day; d-borneol high-dose group (Bor-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day; CDDP group (CDDP, n = 6): intraperitoneal injection of cisplatin (3 mg/kg) every two days; a low-dose combination treatment group (C+B-L, n = 6): intragastric administration of d-borneol (30 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days; a high-dose combination treatment group (C+B-H, n = 6): intragastric administration of d-borneol (60 mg/kg) once a day and intraperitoneal injection of cisplatin (3 mg/kg) every two days. We usually first orally gavage d-borneol, and then inject cisplatin intraperitoneally half an hour later. After 14 days treatment, the samples were obtained from the mice for the further experiments.

    Click to Show/Hide
Response regulation d-borneol in combination with cisplatin induced ferroptosisviaNCOA4-mediated ferritinophagy and also increased the expression levels of ACSL4, regulated PCBP2 and PRNP to promote the conversion of Fe3+to Fe2+, reduced the activity or expression of antioxidants enzymes (GSH and HO-1), and induced ROS accumulation and thereby promoted ferroptosis. In addition, activation of autophagy inhibited progression of the EMT and increased sensitivity to cisplatin in cisplatin-resistant lung cancer cells.
References
Ref 1 d-Borneol enhances cisplatin sensitivity via autophagy dependent EMT signaling and NCOA4-mediated ferritinophagy. Phytomedicine. 2022 Nov;106:154411. doi: 10.1016/j.phymed.2022.154411. Epub 2022 Aug 23.