The ovarian cancer G-protein coupled receptor 1 (OGR1) refers to a form of G protein-coupled receptor (GPCR) that shares almost a similar structure with the other three types of GPCRs, which include GRP4, G2A, and TDAG8, which are known to serve as proton-sensing GPCRs. For the OGR1, its proton-sensing features prevail in bones. The expression of OGR1 becomes evident in osteoblasts and osteoclasts. Here, it usually facilitates acid-induced signaling trails through phospholipase C, G (q/11) protein, IP (3) formation, and the resultant release of Ca2+ from hapsigargin-sensitive stocks. When it comes to acidic pH, it induces the induction of cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2). These lead to the stimulation of osteoclastogenesis and the release of bone calcium. In addition, the OGR1 receptors intercede the influences of the distinct phospholipids. The protein that this protein encodes is a GPCR for sphingosylphosphorylcholine, which is usually active at pH 6.8 while inactive at pH 7.8. The mutations that occur in the gene might lead to amelogenesis imperfecta and illnesses comprising of Iia6 and Hypomaturation. Nonetheless, the idea of whether the regulation of lipid relates to these receptors remains under discussions (Chi, 2014) . For the paper, therefore, it researches the role of the OGR1 receptor in cell proliferation, migration and tumor metastasis, recent generation of knockout animals, and new observations. Empty vector transfected the cells as controls.
Cell Proliferation
Regarding the role that OGR1 plays in cell proliferation, various studies prevail. One such study is on the influences of OGR1 protein on apoptosis and proliferation of the cells affiliated with breast cancer together with its molecular mechanism. Here, the MCF-7 cell line highly revealed that the eukaryotic expression vector’s transient transfection constructed OGR1 while utilizing cancer cells. Empty vector was used to transfect the cells as controls. The result was the influences of high expression of OGR1 on the proliferation, growth, and apoptosis of cells among other abilities. Furthermore, the studies have focused on the influences that highly expressed OGR1 has toward serine-threonine kinase (AKT) in line with other genes. The investigations revealed that in the case of apoptosis experiment, the highly expressed OGR1 prevalent in breast cancer led to an effective rise in cell apoptosis expression. The experiment on cell proliferation indicated that proliferation and growth capabilities of breast cancer cells associated with highly expressed OGR1 were limited to a certain degree when likened to the breast cancer cells with which OGR1 features low expression. Regarding the western blotting results, they revealed that p53 expression levels of protein and gene in breast cancer cells attributed to highly expressed OGR1 rose. No major difference prevailed in the AKT protein expression between cancer cells having high or low expression. Nonetheless, the phosphorylated-AKT (p-AKT’s) protein content for breast cancer cells featuring highly expressed OGR1 was lower compared to those associated with OGR1 at low expression (Zhang, et al., 2019) . Thus, alterations in OGR1 expression influences the apoptosis and proliferation of breast cancer cells, which correlate to p53 and AKT expression to a certain degree.
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Migration and Tumor Metastasis
In understanding the role of OGR1 in migration and tumor metastasis, it is vital to realize that it serves as a proton-sensing receptor that facilitates pH homeostasis. It mediates the actions it undertakes by affiliating with G proteins, which are responsible for stimulating the mobilization of Ca (2+) or the production on inositol phosphate (IP). For metastasis, it entails a process of spreading tumors from key organs to other body areas while it serves as the leading death cause among cancer patient. The OGR1 gene is usually at low metastatic levels when likened to key prostate cancer tissues. For the OGR1, it usually serve as a gene responsible for suppressing metastasis in the event of prostate cancer. For example, an investigation prevails utilizing a mouse metastasis model through which an individual was injected with PC3 metastatic cells of prostate cancer, which had been transfected with empty vector to the athymic’s prostate lobes (Singh, et al., 2007) . The OGR1 gene suppressed metastasis for prostate cancer. It thus contributes to its inhibitory influence on the migration of cells.
Recent Generation of Knockout Animals
To understand the role of OGR1 in recent generation of knockout animals, an investigation was carried out on it modulation of the severity of autoimmunity and in regulation the production of nitric oxide. The OGR1 serves as a protein-sensing molecule, which has the capacity of detecting declines in extracellular pH, which prevails during inflammation. Whereas studies have revealed OGR1 to possess pro-inflammatory functions to a number of illnesses, no investigations prevail regarding the role it plays in autoimmunity. In this sense, a certain study focused on assessing whether OGR1 plays any role when it comes to the production of autoimmunity of the T cell by differentiating the between establishment of experimental autoimmune encephalomyelitis in OGRI-knockout and the wild type mice. For the OGR1-knockout mice, it portrayed a declined clinical illness course that resulted from a major decline in the growth of myelin oligodendrocyte glycoprotein cells. The accumulation of effectors also reduced in the nervous system. In this sense, the responses by the impaired T-cells in the case of the OGR1-knockout mice linked with a declined frequency together with the dendritic cells number in lymph nodes’ draining. The nitric oxide production by the macrophages rose (D'Souza, et al., 2016) . As such, it becomes evident that the OGR1 is crucial when it comes to regulating the responses of the T cells in the event autoimmunity.
New Observation
The new observation witnessed in the area of OGR1 revolves around the role that it plays in the response of the bone to metabolic acidosis. When it comes to severe metabolic acidosis, it stimulates resorption of the bone leading it to lose bicarbonate and calcium. For both osteoclasts and osteoblasts, they sense the OGR1’s H + , while its activation results in a rise in resorption of the bone in line with a reduction in formation of the bone. In an investigation carried out in OGR1-knockout mice, an unanticipated rise prevailed in bone resorption, but nonetheless, a rise in bone volume associated with enhanced formation of the bone (Jorgetti, Drueke, & Ott, 2016) . This realization has opened an avenue for exploring prospective additional anabolic treatment areas in the event of individuals having low bone mass.
An additional recent observation pertaining to OGR1 relates to ways in which it responds to particular benzodiazepines or low extracellular pH. The pleiotropic state attributed to OGR1 signaling in the event of the human airway smooth muscle (HASM) cells reveals that OGR1 would play a critical role in therapeutic process in the case of obstructive lung illnesses. Nevertheless, the fundamental regulatory and pharmacological traits attributed to OGR1 have not yet received sufficient understanding. In fostering increased comprehension, a certain study has emphasized on modelling a system of HASM expressed in an endogenous or heterologous manner in evaluating expression changes, signaling capacities, and subcellular localization after chronic or severe treatment using sulazepam and benzodiazepines lorazepam. Here, the OGR1 internalized rapidly while acute treatment using benzodiazepines failed to interfere with the OGR1 mRNA abundance. Nonetheless, major downregulation prevailed after chronic treatment. From the observation, it became apparent that the capacity of inducing desensitization and internalization of OGR1 depended on the activator (Nayak, et al., 2019) . This reflected the capacity of distinct activators in inducing certain receptor confirmations in line with engaging with key heterotrimeric G proteins.
References
Chi, J. A. (2014). Molecular genetics of dysregulated pH homeostasis. New York: Springer.
D'Souza, C. A., Zhao, F. L., Li, X., XU, Y., Dunn, S. E., & Zhang, L. (2016). OGR1/GPR68 modulates the severity of experimental autoimmune encephalomyelitis and regulates nitric oxide production by macrophages. PLoS One, 11 (2), e0148439.
Jorgetti, V., Drueke, T. B., & Ott, S. M. (2016). Role of proton receptor OGR1 in bone response to metabolic acidosis? Kidney International, 89 (3), 529-531.
Nayak, A. P., Pera, T., Deshpande, D. A., Michael, J. V., Liberato, J. R., Pan, S., . . . Penn, R. B. (2019). An additional recent observation pertaining to OGR1 relates to ways in which it responds to particular benzodiazepines or low extracellular pH. The pleiotropic state attributed to OGR1 signaling in the event of the human airway smooth muscle (HASM) cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 316 (5), L894-L902.
Singh, L. S., Berk, M., Oates, R., Zhao, Z., Tan, H., Kirmani, K., . . . Xu, Y. (2007). Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer. Journal of the National Cancer Institute, 99 (17), 1313-1327.
Zhang, J., Che, L., Sun, W., Shang, J., Hao, M., & Tian, M. (2019). Correlation of OGR1 with proliferation and apoptosis of breast cancer cells. Oncology Letters, 17 (5), 4335-4340.
