G-protein Coupled Receptor 34 Knockdown Impairs the Proliferation and Migration of HGC-27 Gastric Cancer Cells In Vitro

Jin, Zhongtian; Li, Kun; Li, Mei; Ren, Zhigang; Wang, Fushun; Zhu, Jinmin; Leng, Xi-sheng; Yu, Weidong

doi:10.4103/0366-6999.151114

Cited by 16 publications

(19 citation statements)

References 18 publications

(19 reference statements)

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“…In addition, our analyzes revealed targets with less defined roles in placentation with links with placental complications, eg, PLAC4 (", (Tuohey et al, 2013]), and candidates yet to be studied in the context of placental development. For example, BDE-47-induced expression of GPR34 (Figure 5C), which controls aspects of migration in cancer cells (Jin et al, 2015), and may be required for sufficient immune response to pathogens (Liebscher et al, 2011). Our findings, which complement our observations of BDE-47 functional impairment, provide specific pathways with known roles in trophoblast/placental development to be significantly altered with exposure.…”

Section: Discussionsupporting

confidence: 66%

Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts

Robinson

Kapidzic

Hamilton

et al. 2018

Toxicological Sciences

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Despite gradual legislative efforts to phase out flame retardants (FRs) from the marketplace, polybrominated diphenyl ethers (PBDEs) are still widely detected in human maternal and fetal tissues, e.g., placenta, due to their continued global application in consumer goods and inherent biological persistence. Recent studies in rodents and human placental cell lines suggest that PBDEs directly cause placental toxicity. During pregnancy, trophoblasts play key roles in uterine invasion, vascular remodeling and anchoring of the placenta-fetal unit to the mother. Thus, to study the potential consequences of PBDE exposures on human placental development, we used an in vitro model: primary villous cytotrophoblasts (CTBs). Following exposures, the endpoints that were evaluated included cytotoxicity, function (migration, invasion), the transcriptome, and the methylome. In a concentration-dependent manner, common PBDE congeners, BDE-47 and -99, significantly reduced cell viability and increased death. Upon exposures to sub-cytotoxic concentrations (≤ 5µM), we observed BDE-47 accumulation in CTBs with limited evidence of metabolism. At a functional level, BDE-47 hindered the ability of CTBs to migrate and invade. Transcriptomic analyses of BDE-47 effects suggested concentration-dependent changes in gene expression, involving stress pathways, e.g., inflammation and lipid/cholesterol metabolism as well as processes underlying trophoblast fate, e.g., differentiation, migration, and vascular morphogenesis. In parallel assessments, BDE-47 induced low-level global increases in methylation of CpG islands, including a subset that were proximal to genes with roles in cell adhesion/migration. Thus, using a primary human CTB model, we showed that PBDEs induced alterations at cellular and molecular levels, which could adversely impact placental development.

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Section: Discussionsupporting

confidence: 66%

Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts

Robinson

Kapidzic

Hamilton

et al. 2018

Toxicological Sciences

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“…For urothelial cancer, WNT7B, SFRP1, DNAJB2, and ATF3 were reported as target genes with cantharidin predicted as a reversal drug [ 62 ]. Some genes captured in this study have been previously identified for an association with cancer to include CNR2 that is associated with bladder cancer cell growth and motility which is linked to the cannabinoid 2 receptor-mediated modifications [ 63 ], GRR34 knockdown was shown to impair proliferation and migration of HGC-27 gastric cancer cells [ 64 ], DDHD2 as a potential cancer marker in human urine [ 65 ], and BACE2 as a prognostic marker in cervical cancer [ 66 ]. The significance of MAPK signaling, integrin-linked kinase, growth inhibitor family member 2, and NRF2-mediated oxidative stress response pathways provides an important linkage of involvement of oxidative stress and DNA damage after arsenic exposure in human which lead to carcinogenesis through dysregulation of these signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Association between Arsenic Level, Gene Expression in Asian Population, and In Vitro Carcinogenic Bladder Tumor

Singhal

Ruprecht

Sens

et al. 2022

Oxidative Medicine and Cellular Longevity

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The IARC classified arsenic (As) as “carcinogenic to humans.” Despite the health consequences of arsenic exposure, there is no molecular signature available yet that can predict when exposure may lead to the development of disease. To understand the molecular processes underlying arsenic exposure and the risk of disease development, this study investigated the functional relationship between high arsenic exposure and disease risk using gene expression derived from human exposure. In this study, a three step analysis was employed: (1) the gene expression profiles obtained from two diverse arsenic-exposed Asian populations were utilized to identify differentially expressed genes associated with arsenic exposure in human subjects, (2) the gene expression profiles induced by arsenic exposure in four different myeloma cancer cell lines were used to define common genes and pathways altered by arsenic exposure, and (3) the genetic profiles of two publicly available human bladder cancer studies were used to test the significance of the common association of genes, identified in step 1 and step 2, to develop and validate a predictive model of primary bladder cancer risk associated with arsenic exposure. Our analysis shows that arsenic exposure to humans is mainly associated with organismal injury and abnormalities, immunological disease, inflammatory disease, gastrointestinal disease, and increased rates of a wide variety of cancers. In addition, arsenic exerts its toxicity by generating reactive oxygen species (ROS) and increasing ROS production causing the imbalance that leads to cell and tissue damage (oxidative stress). Oxidative stress activates inflammatory pathways leading to transformation of a normal cell to tumor cell specifically; there is significant evidence of the advancing changes in oxidative/nitrative stress during the progression of bladder cancer. Therefore, we examined the relation of differentially expressed genes due to exposure of arsenic in human and bladder cancer and developed a bladder cancer risk prediction model. In this study, integrin-linked kinase (ILK) was one of the most significant pathways identified between both arsenic exposed population which plays a key role in eliciting a protective response to oxidative damage in epidermal cells. On the other hand, several studies showed that arsenic trioxide (ATO) is useful for anticancer therapy although the mechanisms underlying its paradoxical effects are still not well understood. ATO has shown remarkable efficacy for the treatment of multiple myeloma; therefore, it will be helpful to understand the underlying cancer biology by which ATO exerts its inhibitory effect on the myeloma cells. Our study found that MAPK is one of the most active network between arsenic gene and ATO cell line which is involved in indicative of oxidative/nitrosative damage and well associated with the development of bladder cancer. The study identified a unique set of 147 genes associated with arsenic exposure and linked to molecular mechanisms of cancer. The risk prediction model shows the highest prediction ability for recurrent bladder tumors based on a very small subset (NKIRAS2, AKTIP, and HLA-DQA1) of the 147 genes resulting in AUC of 0.94 (95% CI: 0.744-0.995) and 0.75 (95% CI: 0.343-0.933) on training and validation data, respectively.

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“…Cancer cells are frequently used as experimental model in basic and clinical studies. MGC803 and HGC27 cell lines have been used for many years in gastric cancer research, however, the difference of their genetic background have not been reported (Tamura et al, 1996;Zhang et al, 2004;Jin et al, 2015). By global transcriptomics profiling for both cell lines, we characterized the differential expression of genes between these two cell lines.…”

Section: Discussionmentioning

confidence: 99%

Genetic Profiles Affect the Biological Effects of Serine on Gastric Cancer Cells

Xue

Xiang

et al. 2020

Front. Pharmacol.

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A high serine content in body fluid was identified in a portion of patients with gastric cancer, but its biological significance was not clear. Here, we investigated the biological effect of serine on gastric cancer cells. Serine was added into the culture medium of MGC803 and HGC27 cancer cells, and its influence on multiple biological functions, such as cell growth, migration and invasion, and drug resistance was analyzed. We examined the global transcriptomic profiles in these cultured cells with high serine content. Both MGC803 and HGC27 cell lines were originated from male patients, however, their basal gene expression patterns were very different. The finding of cell differentiationassociated genes, ALPI, KRT18, TM4SF1, KRT81, A2M, MT1E, MUC16, BASP1, TUSC3, and PRSS21 in MGC803 cells suggested that this cell line was more poorly differentiated, compared to HGC27 cell line. When the serine concentration was increased to 150mg/ml in medium, the response of these two gastric cancer cell lines was different, particularly on cell growth, cell migration, and invasion and 5-FU resistance. In animal experiment, administration of high concentration of serine promoted cancer cell metastasis to local lymph node. Taken together, we characterized the basal gene expressing profiles of MGC803 and HGC27. The HGC27 cells were more differentiated than MGC803 cells. MGC803 cells were more sensitive to the change of serine content. Our results suggested that the responsiveness of cancer cells to microenvironmental change is associated with their genetic background.

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G-protein Coupled Receptor 34 Knockdown Impairs the Proliferation and Migration of HGC-27 Gastric Cancer Cells In Vitro

Cited by 16 publications

References 18 publications

Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts

Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts

Association between Arsenic Level, Gene Expression in Asian Population, and In Vitro Carcinogenic Bladder Tumor

Genetic Profiles Affect the Biological Effects of Serine on Gastric Cancer Cells

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