Molecule Information

General Information of the Molecule (ID: Mol00607)

• Name: Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) ,Homo sapiens
• Synonyms: hnRNP A1; Helix-destabilizing protein; Single-strand RNA-binding protein; hnRNP core protein A1; HNRPA1
• Molecule Type: Protein
• Gene Name: HNRNPA1
• Gene ID: 3178
• Location: chr12:54280193-54287088[+]
• Sequence:
  MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCVVMRDPNTKRSRGFGFV
  TYATVEEVDAAMNARPHKVDGRVVEPKRAVSREDSQRPGAHLTVKKIFVGGIKEDTEEHH
  LRDYFEQYGKIEVIEIMTDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKA
  LSKQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRGGFGGSRGGGGYGGS
  GDGYNGFGNDGGYGGGGPGYSGGSRGYGSGGQGYGNQGSGYGGSGSYDSYNNGGGGGFGG
  GSGSNFGGGGSYNDFGNYNNQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGYGGS
  SSSSSYGSGRRF
• 3D-structure: PDB ID: 7ZJ2; Classification: Nuclear protein; Method: Electron microscopy; Resolution: 3.32 Å
• Function: Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1. May bind to specific miRNA hairpins.
• Uniprot ID: ROA1_HUMAN
• Ensembl ID: ENSG00000135486
• HGNC ID: HGNC:5031

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.2] [1]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Liver cancer
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.41E-05; Fold-change: 1.29E-01; Z-score: 4.81E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PKM2 mediated glycolysis signaling pathway; Activation; hsa05230
• In Vitro Model: HCCLM3 cells; Liver; Homo sapiens (Human); CVCL_6832
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vivo Model: SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-374b/hnRNPA1/PkM2 axis functions as an important mechanism in sorafenib resistance, with sorafenib-induced miR-374b downregulation and subsequently elevated glycolysis.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Ovarian cancer [ICD-11: 2C73.0] [2]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780/DDP cells; Ovarian; Homo sapiens (Human); N.A.
• In Vitro Model: SKOV3/DDP cells; ovarian; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Immunoprecipitation assay
• Experiment for Drug Resistance: Cell viability assay; Colony formation assay
• Mechanism Description: Our findings demonstrate a significant reduction in O-GlcNAc glycosylation of SRSF2 at Ser101 in cisplatin-resistant cells, suggesting that O-GlcNAc modification may regulate cisplatin resistance through alternative splicing of AUF1 to generate p45 or p37 isoforms mediated by SRSF2. The current study demonstrated that phosphorylation of hnRNPA1 at S95 site was significantly increased in cisplatin-resistant ovarian cancer. In addition, phosphorylation at Ser95 regulated recruitment of hnRNPA1 to AUF1 pre-mRNA to compete with SRSR2. Therefore, the phosphorylation of hnRNPA1 mediated by DNA-PK and O-GlcNAc glycosylation of SRSF2 might potentially regulate the alternative splicing of AUF1 and contribute to cisplatin resistance in ovarian cancer.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.41E-05; Fold-change: 4.93E-01; Z-score: 5.87E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.15E-04; Fold-change: -6.89E-01; Z-score: -6.25E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 3.43E-01; Fold-change: -5.74E-01; Z-score: -8.33E-01

References

• Ref 1: MiR-374b re-sensitizes hepatocellular carcinoma cells to sorafenib therapy by antagonizing PKM2-mediated glycolysis pathway. Am J Cancer Res. 2019 Apr 1;9(4):765-778. eCollection 2019.
• Ref 2: Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin. Cell Oncol (Dordr). 2024 Dec;47(6):2349-2366.