Technology

Myosin regulatory light chain 3 (MRCL3) is a subunit of the myosin regulatory light chain which is though to play a specific role myosin regulation. This gene is coded by four exons and has similar calcium-binding domain to a retinal specific gene, Recoverin, which is involved in visual excitation and light adaption (Dizhoor, 2002). A study on the genomic structure and organization of candidate genes that causes myopia, which is a common eye disorder, showed that MRCL3 is expressed in ocular tissues of myopia patients.

However, mutation screenings showed that induced polymorphism of the gene were not associated with the disease (Scavello et al, 2005). Another study found that MRCL3 may play a role in the regulation of muscle filament assembly and reorganization in muscle cells. The study found that diphosphorylated MRCL3 is necessary for the organization of stress fibers and contractile rings during cell division (Iwasaki et al, 2001).

The role of MRLC3 in cancer is not clear although studies suggest that the function of MRCL3 in cell migration maybe be involved in cell invasion in metastatic cancer (Nguyen, Hussaini  Gonias, 1998 Tohtong et al, 2003). Cancer cell lines treated with inhibitors of myosin light chain kinase (MLCK), which regulates the phosphorylation of MRLC3, showed marked reduction of invasiveness in in vitro invasion assays. The reduction in tumor cell invasion was mainly due to impaired cellular motility (Tohtong et al, 2003). This result is consistent with the stimulation of cell migration in breast cancer cells after treatment with urokinase-type plasminogen activator which stimulates phosphorylation of MRCL3 (Nguyen, Hussaini  Gonias, 1998). While it is apparent that the role of MRLC3 in cell migration is significant in cancer metastasis and invasiveness, other cell functions of MRCL3 may be involved in pathophysiological processes involved in cancer.

Significance of Cyclophilin A in Cancer
Cyclophilin A is a member of the cyclophilin family which is a group of specific binding protein primarily localized in the cytoplasm. Cyclophins are known as the target binding protein for the immunosuppressive agent cyclosporin A (Handschumacher et al, 1984). Cyclophiln A also has enzymatic peptidyl-prolyl cistrans-isomerase (PPIase) activity necessary for protein binding in vivo. This enzymatic activity in cyclophilins is also involved in protein transport, mitochondrial function and pre-mRNA processing (Andreeva, Heads  Green, 2001 Halestrap, Connern, Griffiths  Kerr, 1997 Bourquin et al, 1997).

Cyclophilin A has been reported to be overexpressed in many cancer cells including cancer cells from human pancreatic cancer, oral squamous cancer and non-small cell lung cancer. Its role in cancer cells remains unclear although a study showed that overexpression of cyclophilin A renders cancer cells resistant to hypoxia and cisplatin-induced apoptosis (Choi et al, 2007). The report showed that induction of cyclophilin A was associated with cell hypoxia while its overexpression prevented apoptosis induced by hypoxia and cisplatin. The result suggested that cyclophilin A plays an important role in tumor growth through the suppression of the production of oxygen reactive species and depolarization of membrane potential in the mitochodria. Another study showed that overexpression of cyclophilin A directly stimulates pancreatic cancer cell proliferation through its receptor CD147 (Li et al, 2005).

The role of cyclophin A in glioma cancer cells is not known although overexpression of another member of the cyclophilin family, cyclophin D, has been shown to suppress apoptosis in glioma cancer cell lines (Machida, Ohta  Osada, 2006). Another study showed that cyclophilins were among the up-regulated proteins found in human glioma cell lines treated with an experimental antiglioma agent suggesting that cyclophilin may also play a role in the resistance of glioma cancer cells to drug-induced apoptosis (Bian et al, 2008).