Table 1 RGS family members as potential biomarkers and their role in different tumour types
From: Function and regulation of RGS family members in solid tumours: a comprehensive review
RGS family | RGS member | Tumour | Expression (Compare to normal) | Effects |
|---|---|---|---|---|
RGS A/RZ | RGS17 | Non-small cell lung cancer | Up | Cell proliferation, regulation of the cAMP-PKA-CREB pathway [15, 16] and miRNA-199, miR-203 inter-regulation [21, 22] |
Prostate cancer | Up | Inhibition of AMP kinase, promoting development [13, 15, 16] and miR-203 interactions affecting cell proliferation invasion and migration ability [23] | ||
Ovarian Cancer | Down | Regulation of LPA-mediated AKT activation process [20] | ||
Cervical cancer | Up | Positive correlation with Lincoo483, promotes proliferation and invasion, inhibits apoptosis [19] | ||
Hepatocellular carcinoma | Up | Regulation of cancer cell proliferation, migration and invasion [18] | ||
Colorectal cancer | Up | Promotes growth and migration [17] | ||
RGS19 | Ovarian cancer | Up | Attenuates cell cycle control and enhances AKT signalling [24] | |
Bladder cancer | Up | Significant effect on survival rate [25] | ||
Non-small cell lung cancer | Down | Inhibition of Ras activation-induced tumour formation [26] | ||
RGS20 | Breast cancer | Up | Downregulation of E-calmodulin expression, promoting metastasis [27]. Promotes lymph node metastasis, cancer progression, and is associated with poor prognosis [28] | |
Ovarian cancer | ND | Involvement in MAPK, AKT signalling pathways [29] | ||
Bladder cancer | Up | Activation of NF-κB signalling is associated with cell proliferation migration, overall survival [30] | ||
Hepatocellular carcinoma | Up | Associated with lincRNAs with oncogenic potential role [29] | ||
Melanoma | Up | Downregulation of E-calmodulin expression promotes metastasis [27] | ||
Oral cancer | Up | Reversal of miR-365, Enhances cell viability and motility [31] | ||
RGS B/R4 | RGS1 | Breast cancer | Up | Affects inwards flow of calcium, and activation of ERK and AKT kinases, affects cAMP levels, regulates inwards flow of calcium, and immune escape [32, 33] |
Ovarian cancer | Up | Associated with immune infiltration [34] | ||
Cervical cancer | Up | Affects T-cell activation and significantly correlates with immune infiltration and ICI target expression [35] | ||
Non-small cell lung cancer | Up | Affects inwards flow of calcium, activation of ERK and AKT kinases, immune escape [33] | ||
Melanoma | Up | Value-added migration: with tumour thickness, mitotic rate, presence of damaged vessels; anterior lymph node metastasis [36, 37] | ||
B-cell lymphoma | Up | Impact on overall survival [38] | ||
RGS2 | Breast cancer | Down | Mediates the MCPIP1 pathway to inhibit growth [39]. Negatively correlated with miR-183-5p [40] Mediated Slug regulates epithelial-mesenchymal transition [41] | |
Bladder cancer | Down | Inhibition by UHRF1 is associated with cell proliferation [42] Regulation by ZHX3 affects the migration and invasive ability of tumour cells [43] | ||
Ovarian cancer | Down | Epigenetic changes related to histone modifications and DNA methylation [44]. Regulation of lipopolysaccharide-mediated downstream signalling [45] | ||
Prostate cancer | Down | Growth inhibitory factor, ERK 1/2 is involved; affects androgen-independent tumour cell growth [46, 47] | ||
Non-small cell lung cancer | Down | Degrading transcription factors, a biomarker of proliferative retardation and poor prognosis [48] | ||
Stomach cancer | Up | Significant association with CD8 + T-cell infiltration [49] | ||
Colorectal cancer | Down | Participates in ERK phosphorylation, regulates Rho activity, and affects cell proliferation [50, 51]; has a role in cancer metastasis [52] | ||
Melanoma | Down | Partial effect antagonist, affecting cell proliferation; [53] inhibits MAPK and AKT pathways [54] | ||
Oral cancer | Down | Associated with proliferation of lymphovascular invading cells [55] | ||
Glioblastoma | Down | Stress [56], cell proliferation, migration and invasion are affected by TRPM2-AS expression [57] | ||
RGS3 | Non-small cell lung cancer | Up | Negatively correlated with miR-25 and influences apoptotic cell death [58] | |
Stomach cancer | Up | Negatively regulates microRNA-133a and affects cell proliferation [59] | ||
Hepatocellular carcinoma | Up | Promotes value addition and inhibits apoptosis [60] | ||
RGS4 | Breast cancer | Down | Affects pseudopod formation, affects G protein-coupled receptor signalling, and is associated with migratory invasion [61,62,63] | |
Ovarian cancer | Down | Negative regulation that attenuates LPA-stimulated cell signalling [64] | ||
Thyroid cancer | Down | Interacts with miR-3663-3p and is involved in cell proliferation, apoptosis [65] | ||
Colorectal cancer | Down | Participates in ERK phosphorylation, regulates Rho activity, and affects cell proliferation [50] | ||
Renal cell carcinoma | Down | Associated with P16 and poor prognosis [66] | ||
Non-small cell lung cancer | Down | Proliferation is positively correlated, but migration is not; [67] negative correlation with lymph node metastasis and TNM staging [62] | ||
Glioblastoma | Up | Affects the invasion and migration ability of cancer cells and induces apoptosis [68] Regulates the mTOR signalling pathway [69] | ||
Neuroblastoma | Down | Inhibits 5-HT (1B) receptor coupling; inhibits Akt pathway [70] regulates δ-opioid receptor signalling [71] | ||
RGS5 | Ovarian cancer | Up | Hypoxia reduces the MAPK/ERK signalling pathway [72] and affects the angiogenic microenvironment [73] | |
Thyroid tumours | Up | Physiological modulators of calcium-sensitive receptors [74] | ||
Parathyroid tumour | Up | Inhibition of signalling at calcium-sensitive receptors [75] | ||
Non-small cell lung cancer | Up | Associated with invasion and metastasis; [76] induces apoptosis and affects adhesion capacity [77] | ||
Hepatocellular carcinoma | Up | Induction of epithelial-mesenchymal transition is associated with hepatocyte injury and fibrosis [78] and is involved in the regulation of GSK-3β activity and Wnt/β-catenin signalling [79] | ||
Renal cell carcinoma | Up | Involved in GPCR-mediated signalling [80] and affects angiogenesis [81] | ||
Stomach cancer | ND | Positively correlated with tumour differentiation and negatively correlated with MVD [82, 83] | ||
Pancreatic cancer | Up | Pericyte markers that affect the normalization of the tumour vascular system [84] | ||
RGS8 | ND | ND | ND | |
RGS13 | B-cell lymphoma | Up | A possible novel marker for MCL [85] | |
RGS16 | Breast cancer | Down | Attenuates phosphatidylinositol 3-kinase signalling, affects cell proliferation [86] and is negatively correlated with tumour cell aggressiveness [87] | |
Colorectal cancer | Up | Prognostic markers [88] | ||
Melanoma | Up | Negatively correlated with T-cell stemness-related genes [89] | ||
Pancreatic cancer | Down | Interaction with FosB affects lymph node metastasis and overall survival [90] | ||
Chondrosarcoma | ND | Negatively correlated with miR-181a and growth, angiogenesis and metastasis [91] | ||
Glioblastoma | Down | Activation of the PI3K-AKT pathway affects survival, and epithelial-mesenchymal transition is significantly associated with poor prognosis [92] | ||
RGS18 | ND | ND | ND | |
RGS21 | ND | ND | ND | |
RGS C/R7 | RGS6 | Breast cancer | Down | Activates apoptosis, involved in Bax/Bcl-2, P53 pathway [93, 94], promotes cell apoptosis and inhibits cell growth [95] |
Bladder cancer | Down | Tumour suppressors that promote P53 activation and DNMT1 downregulation [96,97,98] | ||
Ovarian cancer | Down | Negative regulation that attenuates LPA-stimulated cell signalling [64] | ||
Non-small cell lung cancer | Down | Interacts with SMAD4 and inhibits epithelial-mesenchymal transition [97] | ||
Colorectal cancer | Down | Associated with CEA levels, TNM staging, and lymphatic metastasis [99] | ||
Pancreatic cancer | Down | Associated with tumour differentiation, pT classification, and survival [100] | ||
RGS7 | Melanoma | Down | Inhibitory factor, associated with tumour cell anchor growth, migration [101] | |
RGS9 | ND | ND | ND | |
RGS11 | Non-small cell lung cancer | Up | Biomarkers, which play an important role in cancer-related metastasis [102] are associated with advanced and aggressive cancer [103] | |
RGS D/R12 | RGS10 | Colorectal cancer | Down | There is a negative correlation with DNA methylation [104] |
Ovarian cancer | Down | Antagonizes mTOR signalling, cancer cell viability [105, 106]. Related to histone deacetylation and DNA methylation [107, 108] | ||
Neuroblastoma | ND | Involved in the regulation of AKT signalling pathway in relation to cellular self-viability [105] | ||
RGS12 | Prostate cancer | Down | Negative regulation of AKT and MNX1 pathways [109] | |
Oral cancer | Down | Interferes with PTEN phosphorylation and ubiquitination-like modifications that affect cell proliferation and migration [110] | ||
Osteosarcoma | Down | Inhibitory factor, inhibits tumour metastasis [111] | ||
RGS14 | ND | ND | ND |