RRM1 and Associated Diseases

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Backgrounds of RRM1

Ribonucleotide reductase (RR) is a tetramer enzyme that synthesizes deoxyribonucleotides from ribonucleotides for DNA synthesis. RR is encoded by the RRM1 and RRM2 genes, which are two subunits of the RR enzyme. RRM1 gene encodes the regulatory subunit of ribonucleotide reductase, contains 10 axons that code for 792 amino acid proteins and is important in non-small-cell lung cancer (NSCLC). It is located on chromosome segment 11p15.5, a region with a frequent loss of heterozygosity in NSCLC. The product of the RRM1 gene is the key protein involved in the synthesis and repair of DNA by the formation of deoxyribonucleotides and transformation of ribonucleotides to deoxyribonucleotides. RRM1 expression was highest in the small intestine, stomach, and renal cortex, and lowest in the epidermis, trachea, and larynx.

Functions of RRM1

  • The large subunit of human ribonucleotide reductase, RRM1, is involved in the regulation of cell proliferation, cell migration, the development of tumors and metastasis, and the synthesis of deoxyribonucleotides for DNA synthesis. It is also a cellular target for the chemotherapy drug gemcitabine.
  • RRM1 is also the predominant cellular determinant of the efficacy of the nucleoside analog gemcitabine and is also involved in tumor invasiveness and metastasis.
  • RRM1 is reported to influence cell survival, probably through interaction with the phosphatase and tensin homolog (PTEN), which is an inhibitor of cell proliferation, and suppresses cell migration and invasion by reducing the phosphorylation of focal adhesion kinase.

RRM1 functions. Fig.1 RRM1 functions. (Jordheim, 2011)

Different Expression of RRM1 in Diseases

RRM1 is involved in inhibiting cell migration and metastasis. Overexpression of RRM1 in Ras-transformed mouse fibroblasts has been shown to reduce tumor development and metastasis, suggesting that RRM1 is a tumor suppressor. In transgenic lung cancer cells, increased expression of RRM1 protein increases the expression of phosphatase and tensin homolog (PTEN), an inhibitor of cell proliferation, decreases the phosphorylation of focal adhesion kinase; and decreases cell migration and invasiveness. Additionally, overexpression of RRM1 has a protective effect against carcinogen-induced lung tumors, it decreases the formation of metastases, inhibits the development of carcinogen-induced lung tumors, and prolongs survival in tumor-bearing mice. Overexpression of RRM1 has also been associated with gemcitabine resistance. Low expression of this gene is associated with poor survival in patients with non-small cell lung cancer. In addition, high expression of RRM1 in transgenic mice was associated with anticarcinogenic-induced lung tumorigenesis.

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Reference

  1. Jordheim, L.P.; et al. The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. The lancet oncology. 2011, 12(7): 693-702.
For research use only. Not intended for any clinical use.