scholarly journals COX-2 Silencing in Canine Malignant Melanoma Inhibits Malignant Behaviour

2021 ◽  
Vol 8 ◽  
Author(s):  
Tatiany L. Silveira ◽  
Lisa Y. Pang ◽  
Alexandra Di Domenico ◽  
Emerson S. Veloso ◽  
Istéfani L. D. Silva ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Critical Role ◽  
Micro Rna ◽  
Migration And Invasion ◽  
Melanoma Progression ◽  
Oral Melanoma ◽  
Regulated Expression ◽  
Cox 2 ◽  
Canine Melanoma

Metastatic melanoma is a very aggressive form of cancer in both humans and dogs. Dogs primarily develop oral melanoma of mucosal origin. Although oral melanoma in humans is rare, both diseases are highly aggressive with frequent metastases. This disease represents a “One Health” opportunity to improve molecular and mechanistic understanding of melanoma progression. Accumulating evidence suggests that cyclooxygenase-2 (COX-2) may play a critical role in the malignant behaviour of melanoma. In this study we analysed 85 histologically confirmed melanomas from canine patients and showed that COX-2 is overexpressed in both oral and cutaneous melanomas and that COX-2 expression correlates with established markers of poor prognosis. To determine the role of COX-2 in melanoma we developed two melanoma cell lines with stable integration of an inducible doxycycline-regulated expression vector containing a COX-2 targeted micro-RNA (miRNA). Using this system, we showed that cellular proliferation, migration and invasion are COX-2 dependent, establishing a direct relationship between COX-2 expression and malignant behaviour in canine melanoma. We have also developed a powerful molecular tool to aid further dissection of the mechanisms by which COX-2 regulates melanoma progression.

scholarly journals P01.01 The role of exosome miRNA between tumor cells and microglias during the progression of medulloblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii24-iii24
Author(s):  
Q Chang ◽  
L Zhu ◽  
N Li
Keyword(s):  
Tumor Cells ◽  
Critical Role ◽  
Expression Level ◽  
Migration And Invasion ◽  
Specific Marker ◽  
Migration Ability ◽  
Daoy Cell ◽  
Bv2 Cells ◽  
Close Relationship

Abstract BACKGROUND Medulloblastoma (MB) is the most common malignant paediatric brain tumor. Recent studies show that M2 cells were relative more abundant in Shh subtype of MBs compared with other three subtypes. It’s known that M2 cells have close relationship with many tumors’ progression. But if they play any role in the progression of Shh subtype of MB is not yet clear. Many studies demonstrate that exosomes carring miRNAs have close relationship with tumor invasion. The aim of present study is to clarify the role of exosome miRNA between tumor cells and microglias during the progression of Shh subtype of medulloblastoma. MATERIAL AND METHODS Immunofluerescence staining using iNOS and Arg1, which is M1 and M2 specific marker, respectively, was performed in four subtypes of MBs. After coculture of exosomes extracted from Shh subtype of MB cell (DAOY) with microglia cell (BV2), Q-PCR and ELISA assay were done to evaluate the polarization status of the microglia. Transwell and scratch assay were then performed to detect the migration ability of DAOY cell after treatment of exosomes from polirized M2 cells. MiRNA sequencing by Ion Proton technology was then done to analyze the miRNAs expression level between Shh subtype and other subtype of MBs. Transformation assay was used to overexpress and inhibit the expression of these miRNAs respectively to further clarify the role of exosome miRNA in the polarization of BV2 cells. RESULTS M2 cells were observed more abundant than other three subtypes of tumors, supporting that M2 cells play some role in this subtype of MBs. Exosomes of DAOY cells can induce the polarization of M2 cells. The polarized M2 cells can improved the migration and invasion ability of DAOY cell. Dozens of miRNAs were identified with different expression level between Shh subtype of MBs and other subtype of MB cells. Among them, 4 miRNAs were reported to be related with polariztion of M2 in many other lesions. Three of the 4 miRNAs can induce the polarization of M2 in present study. CONCLUSION Our study demonstrated exosome miRNA play a critical role between tumor cells and microglias during the progression of Shh subtype of medulloblastoma.

scholarly journals NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

2020 ◽  
Author(s):  
Hui Guo ◽  
Jianping Zou ◽  
Ling Zhou ◽  
Yan He ◽  
Miao Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Hippo Pathway ◽  
Critical Role ◽  
Xenograft Model ◽  
Migration And Invasion

Abstract Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

The Role of Tumor-related LncRNA PART1 in cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Jinlan Chen ◽  
Enqing Meng ◽  
Yexiang Lin ◽  
Yujie Shen ◽  
Chengyu Hu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Toll Like Receptor ◽  
Non Coding Rna ◽  
Regulated Expression ◽  
The One ◽  
Long Non Coding Rna

Background: As we all know, long non-coding RNA (lncRNA) affects tumor progression, which has caused a great upsurge in recent years. It can also affect the growth, migration, and invasion of tumors. When we refer to the abnormal expression of lncRNA, we will find it associated with malignant tumors. In addition, lncRNA has been proved to be a key targeted gene for the treatment of some diseases. PART1, a member of lncRNA, has been reported as a regulator in the process of tumor occurrence and development. This study aims to reveal the biological functions, specific mechanisms, and clinical significance of PART1 in various tumor cells. Methods: Through the careful search of PUBMED, the mechanisms of the effect of PART1 on tumorigenesis and development are summarized. Results: On the one hand, the up-regulated expression of PART1 plays a tumor-promoting role in tumors, including lung cancer, prostate cancer, bladder cancer and so on. On the other hand, PART1 is down-regulated in gastric cancer, glioma and other tumors to play a tumor inhibitory role. In addition, PART1 regulates tumor growth mainly by targeting microRNA such as miR-635, directly regulating the expression of proteins such as FUS/EZH2, affecting signal pathways such as the Toll-like receptor pathway, or regulating immune cells. Conclusion: PART1 is closely related to tumors by regulating a variety of molecular mechanisms. In addition, PART1 can be used as a clinical marker for the early diagnosis of tumors and plays an important role in tumor-targeted therapy.

scholarly journals Role of Wnt Signaling During In-Vitro Bovine Blastocyst Development and Maturation in Synergism with PPARδ Signaling

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 923
Author(s):  
Tabinda Sidrat ◽  
Abdul Aziz Khan ◽  
Muhammad Idrees ◽  
Myeong-Don Joo ◽  
Lianguang Xu ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Wnt Signaling ◽  
Cellular Proliferation ◽  
Developmental Process ◽  
Critical Role ◽  
Acid Oxidation ◽  
Cell Renewal ◽  
Blastocyst Development ◽  
Bovine Blastocyst

Wnt/β-catenin signaling plays vital role in the regulation of cellular proliferation, migration, stem cells cell renewal and genetic stability. This pathway is crucial during the early developmental process; however, the distinct role of Wnt/β-catenin signaling during pre-implantation period of bovine embryonic development is obscure. Here, we evaluated the critical role of Wnt/β-catenin pathway in the regulation of bovine blastocyst (BL) development and hatching. 6 bromoindurbin-3’oxime (6-Bio) was used to stimulate the Wnt signaling. Treatment with 6-Bio induced the expression of peroxisome proliferator-activated receptor-delta (PPARδ). Interestingly, the PPARδ co-localized with β-catenin and form a complex with TCF/LEF transcription factor. This complex potentiated the expression of several Wnt directed genes, which regulate early embryonic development. Inhibition of PPARδ with selective inhibitor 4-chloro-N-(2-{[5-trifluoromethyl]-2-pyridyl]sulfonyl}ethyl)benzamide (Gsk3787) severely perturbed the BL formation and hatching. The addition of Wnt agonist successfully rescued the BL formation and hatching ability. Importantly, the activation of PPARδ expression by Wnt stimulation enhanced cell proliferation and fatty acid oxidation (FAO) metabolism to improve BL development and hatching. In conclusion, our study provides the evidence that Wnt induced PPARδ expression co-localizes with β-catenin and is a likely candidate of canonical Wnt pathway for the regulation of bovine embryonic development.

The role of procollagen alpha 1 type 1 (Col1A1) on invasion and cellular signaling in glioma cells.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23165-e23165
Author(s):  
Niramol Savaraj ◽  
Shumei Chen ◽  
Chunjing Wu ◽  
Ying-Ying Li ◽  
Medhi Wangpaichitr ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Cellular Proliferation ◽  
Cellular Signaling ◽  
Migration And Invasion ◽  
G1 Arrest ◽  
Low Grade ◽  
Intermediate Grade

e23165 Background: We have previously shown that Procollagen alpha 1 type 1 (Col1A1) is found more in low and intermediate grade glioma and less often in glioblastoma(GBM) (Cancer Invest. 23:577, 2005). We now investigate their role in cellular function. Methods: 4 glioma cell lines: Glioma 1 and U118 express high amount of Col1A1 ( Col1A1+) ; A172 and SW1783 express insignificant amount of Col1A1 ( Col1A1 - ) as the model . All four cell lines express SPARC. Scratch, transwell, and metrigel assay were used to study migration and invasion. Cell cycles were analyzed by flowcytometry. Results: U118 has the highest amount of SPARC followed by A172, SW1783 and Glioma 1. Thus it does not appear to have any relationship between these two proteins which are known as binding partner. Glioma 1 showed the least invasion and migration followed by U118, SW1783 and A172. Thus, Col1A1 expression appear to correlate with invasiveness. To further confirm this, we have silence Col1A1 in Glioma 1 and U118 using both siRNA and shRNA. All clones exhibit more migration and invasion. However, it does not affect both intracellular and extracellular levels of SPARC. Silencing Col1A1 results in increasing G2M arrest; 11% in U118 and 6% in Glioma 1. However it does not affect cellular proliferation. To further verify this, we have overexpressed Col1A1 in A172 and SW1783 using plasmid containing Col1A1 and DDK tag. These Col1A1 (+) A172 and SW1783 transfectants exhibit less migration and invasion. However, there is no effect on SPARC levels. These Col1A1 positive cells exhibit 12% increase in Go/G1 arrest and decrease in proliferation. A limited protein array also showed that silencing Col1A1 increase in STAT3, 5 and 6 and AKT levels. Interestingly, a difference in sensitivity to STAT3/5 inhibitors also noted in parental and their Col1A1 knock down transfectants. Conclusions: our results support the role of Col1A1 in glioma cell invasiveness, and hence confirm our previous data which showed that Col1A1 is found more in low grade and intermediate grade glioma. Thus, Col1A1 could be an additional useful marker to assess the aggressiveness of GBM beside histopathological grading. Col1A1 may also play a role in cellular signaling pathway.

Inhibition of hypoxia-inducible factor-1α by PX-478 as a potential targeted therapy in ESCC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14083-e14083
Author(s):  
Yingming Zhu ◽  
Yuanwei Zang ◽  
Minghuan Li ◽  
Jinming Yu
Keyword(s):  
Targeted Therapy ◽  
Hypoxia Inducible Factor ◽  
Radical Resection ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Hypoxia Inducible Factor 1Α ◽  
Polymerase Chain ◽  
Cox 2

e14083 Background: Hypoxia is a unique microenvironment in solid tumors, including ESCC. We aim to investigate the interaction between hypoxia-inducible factor-1α (HIF-1α), COX-2 and programmed cell death ligand-1 (PD-L1) and uncover the role of HIF-1α inhibitor PX-478 as a potential targeted therapy in ESCC. Methods: Immunohistochemical staining was performed to investigate the levels of HIF-1α, COX-2 and PD-L1 from 133 pT3N0M0 ESCC patients after radical resection. The prognostic value of the expression of HIF-1α, COX-2 and PD-L1 and the correlation with clinicopathologic features was evaluated. Knockdown assay, CCK-8 assay, Western blot, real-time polymerase chain reaction (RT-PCR), flow cytometry and Transwell migration assays were used in cells experiment. Results: HIF-1α and PD-L1 are independent prognostic factors in pT3N0M0 ESCC. Further data showed that HIF-1α plays an important role in regulation of COX-2 and PD-L1 expression. Our in vitro studies demonstrated that HIF-1α inhibitor, PX-478, induced G2 phase arrest, increased apoptosis, and inhibited migration and invasion of esophageal carcinoma cells, and thus significantly inhibit ESCC cells proliferation. Conclusions: Our results provide new insight into the potential role of HIF-1α inhibitors, PX-478 and open up the possibility of PX-478 for targeted therapy of ESCC.

scholarly journals AUF1 Promotes Proliferation and Invasion of Thyroid Cancer via Downregulation of ZBTB2 and Subsequent TRIM58

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Du ◽  
Jia-Mei Wang ◽  
Da-Lin Zhang ◽  
Tong Wu ◽  
Xiao-Yan Zeng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Binding Sites ◽  
Critical Role ◽  
Common Type ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Thyroid Cancer Cells ◽  
Proliferation And Invasion

The pathogenesis of papillary thyroid cancer (PTC), the most common type of thyroid cancer, is not yet fully understood. This limits the therapeutic options for approximately 7% of invasive PTC patients. The critical role of AUF1 in the progression of thyroid cancer was first reported in 2009, however, its molecular mechanism remained unclear. Our study used CRISPR/Cas 9 system to knockdown AUF1 in IHH4 and TPC1 cells. We noticed that the expression of TRIM58 and ZBTB2 were increased in the AUF1 knockdown IHH4 and TPC1 cells. When TRIM58 and ZBTB2 were inhibited by small hairpin RNAs (shRNAs) against TRIM58 (shTRIM58) and ZBTB2 (shZBTB2), respectively, the proliferation, migration, and invasion ability of the AUF1-knockdown IHH4 and TPC1 cells were increased. In addition, two ZBTB2 binding sites (-719~-709 and -677~-668) on TRIM58 promoter and two AUF1 binding sites (1250-1256 and 1258-1265) on ZBTB2 3’-UTR were identified. These results suggested that AUF1 affecting thyroid cancer cells via regulating the expression of ZBTB2 and TRIM58.

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