Gamma-Glutamylcyclotransferase: A Novel Target Molecule for Cancer Diagnosis and Treatment

Gamma-glutamylcyclotransferase (GGCT) is one of the major enzymes involved in glutathione metabolism. However, its gene locus was unknown for many years. Recently, the gene for GGCT was found to be identical to C7orf24, which is registered as a hypothetical protein. Orthologs have been found in bacteria, plants, and nematodes as well as higher organisms, and the GGCT gene is highly preserved among a wide range of species. GGCT (C7orf24) was also reported as an upregulated protein in various cancers. Although the function of GGCT in cancer cells has not been determined, the following important activities have been reported: (1) high expression in various cancer tissues and cancer cell lines, (2) low expression in normal tissues, (3) inhibition of cancer cell proliferation via anti-GGCT RNAi, (4) inhibition of cancer cell invasion and migration via anti-GGCT RNAi, (5) an epigenetic transcriptional regulation in cancer cells, and (6) an antitumor effect in cancer-bearing xenograft mice. Therefore, GGCT is promising as a diagnostic marker and a therapeutic target for various cancers. This review summarizes these interesting findings.

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MiR-1-3p Suppresses the Proliferation, Invasion and Migration of Bladder Cancer Cells by Up-Regulating SFRP1 Expression

Cellular Physiology and Biochemistry ◽

10.1159/000464379 ◽

2017 ◽

Vol 41 (3) ◽

pp. 1179-1188 ◽

Cited By ~ 13

Author(s):

Anquan Shang ◽

Man Yang ◽

Fujun Shen ◽

Jun Wang ◽

Jun Wei ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Migration Ability ◽

Invasion And Migration ◽

Over Expression ◽

Normal Tissues ◽

Sfrp1 Expression ◽

Bladder Cancer Cells ◽

And Migration ◽

Cancer Tissues

Background: Bladder cancer is of compelling morbidity and mortality due to its high recurrence rate. Little development has been made in the last decades in the therapy methods. Thus, the mechanism of its growth and invasiveness involving novel molecular targets are needed. Objective: Our research objective is to confirm the hypothesis that miR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells. Methods: The expression levels of miR-1-3p and SFRP1 were evaluated using RT-qPCR in bladder cancer tissues and cells as well as in normal tissues and cells. J82 cell lines were selected as experiment subjects due to their low expression levels of miR-1-3p. Plasmids carrying miR-1-3p mimics, miR-1-3p inhibitors and SFRP1 were transfected into the J82 cell lines. Subsequently, the protein expression of SFRP1 was detected using Western Blot analysis, and cell proliferation, apoptosis, invasion and migration ability was measured using MTT, the flow cytometry, the Transwell test and wound healing assays, respectively Results: Bladder cancer tissues and cells exhibited significant decrease in the expression of miR-1-3p and SFRP1 compared to normal tissues and cells, and human bladder cancer cell line J82 exhibited the most significant decrease in these expressions (P < 0.05). MiR-1-3p up-regulates SFRP1 expression in bladder cancer cells, and the over-expression of miR-1-3p can suppress the proliferation, invasion and migration ability of bladder cancer cells. This mechanism is similar to the effect of SFRP1 over-expression on bladder cancer cells. Conclusion: MiR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells by up-regulating SFRP1 expression.

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The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

Cellular Physiology and Biochemistry ◽

10.1159/000480419 ◽

2017 ◽

Vol 43 (1) ◽

pp. 405-418 ◽

Cited By ~ 46

Author(s):

Yaoyao Xiong ◽

Long Wang ◽

Yuan Li ◽

Minfeng Chen ◽

Wei He ◽

...

Keyword(s):

Bladder Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Cancer Growth ◽

Invasion And Migration ◽

Non Coding Rna ◽

Bladder Cancer Cells ◽

And Migration ◽

Cancer Tissues ◽

Long Non Coding Rna

Backgrounds/Aims: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

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miR-142-3p Modulates Cell Invasion and Migration via PKM2-Mediated Aerobic Glycolysis in Colorectal Cancer

Analytical Cellular Pathology ◽

10.1155/2021/9927720 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

JunYu Ren ◽

Wenliang Li ◽

Guoqing Pan ◽

Fengchang Huang ◽

Jun Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

Pyruvate Kinase ◽

Cancer Cell ◽

Cell Invasion ◽

Aerobic Glycolysis ◽

Cancer Cell Invasion ◽

Human Colorectal Cancer ◽

Invasion And Migration ◽

And Migration ◽

Cancer Tissues

Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.

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Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508

Integrative Cancer Therapies ◽

10.1177/15347354211062639 ◽

2021 ◽

Vol 20 ◽

pp. 153473542110626

Author(s):

Peng Bian ◽

Chuan Liu ◽

Wei Hu ◽

Yu Ding ◽

Shusheng Qiu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Antitumor Effect ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Invasion And Migration ◽

Anticancer Effects ◽

And Migration ◽

Cancer Tissues

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

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MiR-1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial-Mesenchymal Transition by Targeting DCLK3

Frontiers in Oncology ◽

10.3389/fonc.2021.688882 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yibin Zhao ◽

Hongyi Zhou ◽

Jie Shen ◽

Shaohui Yang ◽

Ke Deng ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Qrt Pcr ◽

And Migration ◽

Cancer Tissues

BackgroundDysregulated microRNAs (miRNAs) are common in human cancer and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, this study aimed to evaluate the expression and biological function of miR-1236-3p in colon cancer.MethodsThis study screened the miRNA in normal and colon cancer tissues through array analysis. In addition, quantitative Reverse Transcription–Polymerase Chain Reaction (qRT-PCR) analysis was performed to validate the expression of miR-1236-3p in normal and tumor tissues from colon cancer patients and cancer cell lines. Online predicting algorithms and luciferase reporter assays were also employed to confirm Doublecortin Like Kinase 3 (DCLK3) was the target for miR-1236-3p. Moreover, the impact of miR-1236-3p on the progression of colon cancer was evaluated in vitro and in vivo. Western blotting and qRT-PCR were also performed to investigate the interactions between miR-1236-3p and DCLK3.ResultsMiR-1236-3p was significantly downregulated in colon cancer tissues and its expression was associated with the TNM stage and metastasis of colon. In addition, the in vitro and in vivo experiments showed that miR-1236-3p significantly promoted cancer cell apoptosis and inhibited the proliferation, invasion, and migration of cancer cells. The results also showed that miR-1236-3p hindered Epithelial–mesenchymal Transition (EMT) by targeting DCLK3. Moreover, the expression of DCLK3 mediated the effects of miR-1236-3p on the progression of cancer.ConclusionsMiR-1236-3p functions as a tumor suppressor in colon cancer by targeting DCLK3 and is therefore a promising therapeutic target for colon cancer.

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Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling

Frontiers in Oncology ◽

10.3389/fonc.2021.728583 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tao Qin ◽

Jie Li ◽

Ying Xiao ◽

Xueni Wang ◽

Mengyuan Gong ◽

...

Keyword(s):

Pancreatic Cancer ◽

Sciatic Nerve ◽

Cancer Cells ◽

Cancer Cell ◽

Neurotrophic Factors ◽

Perineural Invasion ◽

Invasion And Migration ◽

Pancreatic Cancer Cells ◽

And Migration

BackgroundPerineural invasion (PNI) is an important pathologic feature of pancreatic cancer, and the incidence of PNI in pancreatic cancer is 70%-100%. PNI is associated with poor outcome, metastasis, and recurrence in pancreatic cancer patients. There are very few treatments for PNI in pancreatic cancer. Honokiol (HNK) is a natural product that is mainly obtained from Magnolia species and has been indicated to have anticancer activity. HNK also has potent neurotrophic activity and may be effective for suppressing PNI. However, the potential role of HNK in the treatment of PNI in pancreatic cancer has not been elucidated.MethodsIn our study, pancreatic cancer cells were treated with vehicle or HNK, and the invasion and migration capacities were assessed by wound scratch assays and Transwell assays. A cancer cell-dorsal root ganglion coculture model was established to evaluate the effect of HNK on the PNI of pancreatic cancer. Western blotting was used to detect markers of EMT and neurotrophic factors in pancreatic tissue. Recombinant TGF-β1 was used to activate SMAD2/3 to verify the effect of HNK on SMAD2/3 and neurotrophic factors. The subcutaneous tumor model and the sciatic nerve invasion model, which were established in transgenic engineered mice harboring spontaneous pancreatic cancer, were used to investigate the mechanism by which HNK inhibits EMT and PNI in vivo.ResultsWe found that HNK can inhibit the invasion and migration of pancreatic cancer cells. More importantly, HNK can inhibit the PNI of pancreatic cancer. The HNK-mediated suppression of pancreatic cancer PNI was partially mediated by inhibition of SMAD2/3 phosphorylation. In addition, the inhibitory effect of HNK on PNI can be reversed by activating SMAD2/3. In vivo, we found that HNK can suppress EMT in pancreatic cancer. HNK can also inhibit cancer cell migration along the nerve, reduce the damage to the sciatic nerve caused by tumor cells and protect the function of the sciatic nerve.ConclusionOur results demonstrate that HNK can inhibit the invasion, migration, and PNI of pancreatic cancer by blocking SMAD2/3 phosphorylation, and we conclude that HNK may be a new strategy for suppressing PNI in pancreatic cancer.

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Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1488-1 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 7

Author(s):

Shuangjian Jiang ◽

Chengqiang Mo ◽

Shengjie Guo ◽

Jintao Zhuang ◽

Bin Huang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Proliferation ◽

Prostate Cancer Cells ◽

Invasion And Migration ◽

And Migration

Abstract Background Human bone marrow mesenchymal stem cells (hBMSCs) are implicated in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the physiological mechanisms by which exosomal miR-205 derived from hBMSCs may modulate the growth of prostate cancer cells. Methods Microarray-based gene expression profiling of prostate cancer was adopted to identify differentially expressed genes and regulatory miRNAs, which identified the candidates RHPN2 and miR-205 as the study focus. Then the binding affinity between miR-205 and RHPN2 was identified using in silico analysis and luciferase activity detection. Prostate cancer cells were co-cultured with exosomes derived from hBMSCs treated with either miR-205 mimic or miR-205 inhibitor. Subsequently, prostate cancer cell proliferation, invasion, migration, and apoptosis were detected in vitro. The effects of hBMSCs-miR-205 on tumor growth were investigated in vivo. Results miR-205 was downregulated, while RHPN2 was upregulated in prostate cancer cells. RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2. Next, experiments demonstrated that hBMSCs-derived exosomes carrying miR-205 contributed to repressed prostate cancer cell proliferation, invasion, and migration and enhanced apoptosis. Furthermore, in vivo assays confirmed the inhibitory effects of hBMSCs-derived exosomal miR-205 on prostate cancer. Conclusion The hBMSCs-derived exosomal miR-205 retards prostate cancer progression by inhibiting RHPN2, suggesting that miR-205 may present a predictor and potential therapeutic target for prostate cancer.

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Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells

Cancer Cell International ◽

10.1186/s12935-019-1076-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Shiwei Liu ◽

Jingchao Li ◽

Liang Kang ◽

Yueyang Tian ◽

Yuan Xue

Keyword(s):

Tumor Growth ◽

Osteosarcoma Cell ◽

Loss Of Function ◽

Osteosarcoma Cells ◽

Invasion And Migration ◽

Normal Tissues ◽

Novel Target ◽

And Migration

Abstract Background Over the years, long non-coding RNAs (lncRNAs) have been clarified in malignancies, this research was focused on the role of lncRNA cartilage injury-related (lncRNA-CIR) in osteosarcoma cells. Methods LncRNA-CIR expression in osteosarcoma tissues and cells, and adjacent normal tissues and normal osteoblasts was determined, then the relations between lncRNA-CIR expression and the clinicopathological features, and between lncRNA-CIR expression and the prognosis of osteosarcoma patients were analyzed. Moreover, the MG63 and 143B cells were treated with silenced or overexpressed lncRNA-CIR, and then the proliferation, invasion, migration and apoptosis of the cells were evaluated by gain- and loss-of-function approaches. The tumor growth, and proliferation and apoptosis of osteosarcoma cells in vivo were observed by subcutaneous tumorigenesis in nude mice. Results We have found that lncRNA-CIR was up-regulated in osteosarcoma tissues and cells, which was respectively relative to adjacent normal tissues and normal osteoblasts. The expression of lncRNA-CIR was evidently correlated with disease stages, distant metastasis and differentiation of osteosarcoma patients, and the high expression of lncRNA-CIR indicated a poor prognosis. Furthermore, the reduction of lncRNA-CIR could restrict proliferation, invasion and migration, but promote apoptosis of osteosarcoma cells in vitro. Meanwhile, inhibited lncRNA-CIR also restrained tumor growth and osteosarcoma cell proliferation, whereas accelerated apoptosis of osteosarcoma cells in vivo. Conclusion We have found in this study that the inhibited lncRNA-CIR could decelerate proliferation, invasion and migration, but accelerate apoptosis of osteosarcoma cells, which may provide a novel target for osteosarcoma treatment.

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Radixin Enhances Colon Cancer Cell Invasion by Increasing MMP-7 Production via Rac1-ERK Pathway

The Scientific World JOURNAL ◽

10.1155/2014/340271 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Qi-Hong Jiang ◽

Ai-Xiang Wang ◽

Yan Chen

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

Colon Cancer Cell ◽

Erk Pathway ◽

Colon Cancer Cells ◽

Cancer Cell Invasion ◽

Invasion And Migration ◽

And Migration

As a member of the ezrin-radixin-moesin (ERM) family, radixin is overexpressed in many tumor tissues. However, little is known about its role in the progression of colon cancer. So we here aimed to determine the function of radixin in colon cancer cell invasion. Interestingly, we found that the expression of radixin was significantly elevated in colon cancer cells. Knockdown of radixin suppressed the invasion and migration of colon cancer cells. Further, knockdown of radixin inhibited the activation of Rac1 and ERK1/2, and decreased the expression and secretion of MMP-7. In addition, Rac1-ERK signaling pathway was required for the radixin-promoted invasion and MMP-7 production. Together, our findings suggest that radixin enhances the invasion and migration of colon cancer cells. Activation of Rac1-ERK pathway and consequent upregulation of MMP-7 production may contribute to the function of radixin in the regulation of colon cancer cell invasion. Thus, radixin may act as a novel target for the diagnosis and treatment of colon cancer.

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Silencing of Sphingosine 1-Phosphate Receptors and Potassium Channels May Inhibits the Invasion and Migration of Breast Cancer

10.21203/rs.3.rs-322090/v1 ◽

2021 ◽

Author(s):

Didem Turgut Cosan ◽

Ahu SOYOCAK ◽

İbrahim Uğur ÇALIŞ

Keyword(s):

Breast Cancer ◽

Potassium Channels ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Invasion And Migration ◽

Sphingosine 1 Phosphate ◽

And Migration ◽

Mcf 7

Abstract Molecular receptor signaling mechanisms play an important role in many pathophysiological processes, including breast cancer. The spread of cancer from peripheral tissue to distant organs by metastasis is the cause of death of most breast cancer patients. For that reason, the most important step in the treatment of cancer is to prevent metastasis. Sphingosine-1-phosphate receptors and potassium channels play role of cancer cell migration, invasion and they may interact with each other in the progression of cancer. In this study, it was aimed to determine the effects of combined silencing of receptors and channels on the invasion and migration of MCF-7 and MDA-MB-231 breast cancer cells and their interactions on cells. We examined the expression levels of S1P1, S1P3, Kv1.3, and Kv10.1 in MCF-7 and MDA-MB-231 breast cancer cell lines by qRT-PCR. The effects of migration and invasion of breast cancer cells were determined through invasian and wound healing assays. It was observed that high invasion and lateral motility in cells decreased with the combined silencing of S1P1, S1P3, Kv1.3 and Kv10.1 in both cell types. It has been determined that silencing the receptors and channels together is more effective than silencing individually. Our data demonstrated the roles of S1P receptors and potassium channels were associated with invasion and migration signaling pathway. Therefore, these are might be possible therapeutic target for breast cancer metastasis.

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