CSN6 promotes melanoma proliferation and metastasis by controlling the UBR5-mediated ubiquitination and degradation of CDK9

AbstractAs a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression, but its biological functions and molecular mechanisms in melanoma remain unknown. Our study showed that CSN6 expression was upregulated in melanoma patients and cells, and correlated with poor survival in melanoma patients. In melanoma cells, CSN6 knockdown remarkably inhibited cell proliferation, tumorigenicity, migration, and invasion, whereas CSN6 recovery rescued the proliferative and metastatic abilities. Notably, we identified that CSN6 stabilized CDK9 expression by reducing CDK9 ubiquitination levels, thereby activating CDK9-mediated signaling pathways. In addition, our study described a novel CSN6-interacting E3 ligase UBR5, which was negatively regulated by CSN6 and could regulate the ubiquitination and degradation of CDK9 in melanoma cells. Furthermore, in CSN6-knockdown melanoma cells, UBR5 knockdown abrogated the effects caused by CSN6 silencing, suggesting that CSN6 activates the UBR5/CDK9 pathway to promote melanoma cell proliferation and metastasis. Thus, this study illustrates the mechanism by which the CSN6-UBR5-CDK9 axis promotes melanoma development, and demonstrate that CSN6 may be a potential biomarker and anticancer target in melanoma.

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microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-κB

Oncotarget ◽

10.18632/oncotarget.9421 ◽

2016 ◽

Vol 7 (22) ◽

pp. 31663-31680 ◽

Cited By ~ 42

Author(s):

Keith M. Giles ◽

Rikki A.M. Brown ◽

Clarissa Ganda ◽

Melissa J. Podgorny ◽

Patrick A. Candy ◽

...

Keyword(s):

Cell Proliferation ◽

Melanoma Cell ◽

Melanoma Cell Proliferation ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

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LncRNA PCAT18/miR-301a/TP53INP1 axis is involved in gastric cancer cell viability, migration and invasion

The Journal of Biochemistry ◽

10.1093/jb/mvaa079 ◽

2020 ◽

Vol 168 (5) ◽

pp. 547-555

Author(s):

Jin Dou ◽

Daoyuan Tu ◽

Haijian Zhao ◽

Xiaoyu Zhang

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cell Viability ◽

Cell Lines ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Invasion And Migration ◽

Proliferation And Metastasis ◽

And Migration ◽

Cell Proliferation And Metastasis

Abstract MiR-301a is as an oncogene involved in the regulation of gastric cancer (GC) progression, but the underlying mechanism is unclear. This study was to explore the lncRNA PCAT18/miR-301a/TP53INP1 axis in regulating the GC cell proliferation and metastasis. In the present study, GC tissues and cell lines were collected for the detection of PCAT18 expression. Herein, we found that PCAT18 is significantly decreases in human GC tissues and five GC cell lines. Overexpression of PCAT18 inhibits cell viability, invasion and migration of GC cells and tumour growth of GC xenograft tumours. PCAT18 negatively regulates the expression level of miR-301a. The interaction between PCAT18 and miR-301a is confirmed by RIP and RNA pull down. MiR-301a mimic increases cell viability and promotes cell migration and invasion and reverses the inhibitory action of PCAT18. TP53INP1 expression is negatively regulated by miR-301a and TP53INP1/miR-301a is involved in GC viability, migration and invasion. The promoting of PCAT18 on TP53INP1 expression is abolished by miR-301a overexpression. In conclusion, lncRNA PCAT18 acts as a tumour suppressor for GC and lncRNA PCAT18, miR-301a and TP53INP1 comprise a signal axis in regulating GC cell proliferation, migration and invasion.

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Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis

Cancer Gene Therapy ◽

10.1038/s41417-020-00274-5 ◽

2020 ◽

Author(s):

Xiang-jun Chen ◽

Sha Liu ◽

Dong-mei Han ◽

De-zhi Han ◽

Wei-jing Sun ◽

...

Keyword(s):

Cell Proliferation ◽

Melanoma Cell ◽

Molecular Mechanisms ◽

Ectopic Expression ◽

Therapeutic Targets ◽

Mapk Signaling ◽

Migration And Invasion ◽

Functional Assays ◽

Melanoma Cell Proliferation ◽

Signaling Axis

AbstractMelanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in melanoma. We identified RP11-705C15.3, a regulator of miR-145-5p, as an oncogenic lncRNA in melanoma. RP11-705C15.3 competitively bound miR-145-5p, relieved the repressive roles of miR-145-5p on its target NRAS, upregulated NRAS expression, and activated MAPK signaling. In vitro functional assays revealed that ectopic expression of RP11-705C15.3 promoted melanoma cell proliferation, inhibited apoptosis, and promoted migration and invasion. Silencing of RP11-705C15.3 repressed melanoma cell proliferation, induced apoptosis, and repressed migration and invasion. Notably, the roles of RP11-705C15.3 in melanoma cell proliferation, apoptosis, migration and invasion are reversed by miR-145-5p overexpression. In vivo functional assays revealed that RP11-705C15.3 promoted melanoma tumor growth and metastasis, which were also reversed by miR-145-5p overexpression. Furthermore, we investigated the expression of RP11-705C15.3 in clinical melanoma tissues and found that RP11-705C15.3 was increased in melanoma tissues. High expression of RP11-705C15.3 was positively correlated with thickness, ulceration, metastasis, and inferior overall survival. Taken together, our findings suggest RP11-705C15.3 as a novel oncogene in melanoma, and highlight that the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis may be potential therapeutic targets for melanoma.

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Polydatin Inhibits Cell Viability, Migration, and Invasion Through Suppressing the c-Myc Expression in Human Cervical Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.587218 ◽

2021 ◽

Vol 9 ◽

Author(s):

Longchang Bai ◽

Yingkang Ma ◽

Xue Wang ◽

Qiongni Feng ◽

Zhining Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Protective Effects ◽

Mesenchymal Transition ◽

Cyclin E1 ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis ◽

Human Cervical Cancer

Polydatin, an active ingredient from the roots of Polygonum cuspidatum, is considered to have protective effects on the cardiovascular system and liver. In this study, we demonstrated that polydatin has antitumor activity against human cervical cancer. Polydatin efficiently inhibited cervical cancer cell proliferation by regulating cell cycle-related proteins including p21, p27, CDK2, CDK4, Cyclin D1, and Cyclin E1. Furthermore, polydatin suppressed cell invasion and migration by regulating epithelial–mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, Snail and Slug. The c-Myc, as a proto-oncogene, is considered to be closely associated with the proliferation and metastasis of tumor cells. After polydatin treatment, the protein expression of c-Myc showed a significant decrease. Based on these data, we overexpressed c-Myc in cervical cancer cells and observed that the overexpression of c-Myc rescued the inhibitory effect of polydatin on cell proliferation and metastasis. These results indicated that polydatin can inhibit cell proliferation and metastasis through suppressing the c-Myc expression in human cervical cancer.

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MiR-200b-3p Functions as an Oncogene by Targeting ABCA1 in Lung Adenocarcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033819892590 ◽

2019 ◽

Vol 18 ◽

pp. 153303381989259 ◽

Cited By ~ 2

Author(s):

Keqiang Liu ◽

Weiqiang Zhang ◽

Jian Tan ◽

Jingbo Ma ◽

Jing Zhao

Keyword(s):

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Adenosine Triphosphate ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Adenocarcinoma Cell ◽

Matrigel Invasion ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

Objective: The aim of this study was to investigate the microRNA-200b-3p expression in lung adenocarcinoma and the possible functional associations of microRNA-200b-3p with cell proliferation, migration, and invasion. Methods: Quantitative real-time polymerase chain reaction was used to detect the expression of microRNA-200b-3p in lung adenocarcinoma samples and in the human lung adenocarcinoma cell lines A549 and H1299. A549 and H1299 cells were transfected with either a microRNA-200b-3p mimic or a negative control microRNA or either an empty vector or an adenosine triphosphate-binding cassette transporter A-1 overexpression vector. A Cell Counting Kit-8 assay was employed to assess the ability of cell proliferation. Transwell assays and transwell-Matrigel invasion assay were, respectively, utilized to assess the capacity of migration and invasion in A549 and H1299 cells. Results: The results showed that microRNA-200b-3p expression was significantly upregulated in tumor tissues compared with that in adjacent normal tissues. Overexpression of microRNA-200b-3p promoted lung adenocarcinoma cell proliferation and metastasis. Furthermore, adenosine triphosphate-binding cassette transporter A-1 was a direct target of microRNA-200b-3p, and this binding was verified by luciferase reporter analysis. Overexpression of adenosine triphosphate-binding cassette transporter A-1 obviously suppressed lung adenocarcinoma cell proliferation, migration, and invasion. Lung adenocarcinoma cell phenotypes induced by microRNA-200b-3p overexpression could be partially remitted by the co-overexpression of microRNA-200b-3p and adenosine triphosphate-binding cassette transporter A-1. Conclusion: This study first identified that microRNA-200b-3p is upregulated in lung adenocarcinoma cells and associated with cell proliferation and metastasis. MicroRNA-200b-3p promoted lung adenocarcinoma cell proliferation and metastasis by suppressing adenosine triphosphate-binding cassette transporter A-1. MicroRNA-200b-3p may function as a novel molecular marker and therapeutic target for lung adenocarcinoma treatment.

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LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer

Cell Death and Disease ◽

10.1038/s41419-021-03921-3 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Jian Xu ◽

Jie Wang ◽

Zhiwei He ◽

Peng Chen ◽

Xueyi Jiang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Target Genes ◽

Erk Signaling ◽

Pcr Analysis ◽

Cell Growth And Migration ◽

Mesenchymal Transition ◽

Potential Biomarker ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

AbstractLncRNAs play essential regulatory roles in pancreatic cancer (PC) tumorigenesis and progression. We aimed to investigate the role of lncRNA CERS6-AS1 in PC. CERS6-AS1 expression was determined in PC tissues and cell lines by PCR analysis. The roles of CERS6-AS1 on proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) were confirmed via CCK-8 assay, EDU assay, transwell assay, wound healing assay, and western blot assay. Besides, the interaction between CERS6-AS1 and their target genes was verified by luciferase report assays and RIP assays. Animal assays and clinical data analysis were performed to validate the functions in vivo. We found that lncRNA CERS6-AS1 was highly expressed in PC tissues and cells. Additionally, high expression of CERS6-AS1 was obviously associated with poor prognosis. Functional assays demonstrated that CERS6-AS1 downregulation significantly inhibited PC cell growth and migration. Moreover, CERS6-AS1 exerted as a molecular sponge for miR-217-5p (miR-217), and miR-217 was confirmed as a potential target of CERS6-AS1. Subsequently, miR-217 suppressed PC cell proliferation and metastasis by directly targeting YWHAG, which interacted with RAF1 and promoted its phosphorylation, leading to RAF1-mediated ERK signaling activation and translocation of phosphorylated ERK from the cytoplasm to the nucleus. Mechanically, CERS6-AS1 silencing significantly inhibited PC cell proliferation and metastasis via a miR-217/YWHAG/RAF1 signaling axis. CERS6-AS1 exerts as a carcinogen in PC to promote malignant features and behaves as a competitive endogenous RNA for miR-217. We identified CERS6-AS1 as a potential biomarker or therapeutic target to improve PC diagnosis and treatment outcomes.

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WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway

Open Life Sciences ◽

10.1515/biol-2021-0096 ◽

2021 ◽

Vol 16 (1) ◽

pp. 920-929

Author(s):

Zhou Cai ◽

Yan Mei ◽

Xiaoye Jiang ◽

Xingfeng Shi

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Migration And Invasion ◽

Cell Cycles ◽

Cell Metastasis ◽

Colorectal Cancer Cells ◽

High Incidence ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis ◽

Hct116 Cells

Abstract Colon cancer (CRC) is a common type of cancer and has a high incidence worldwide. Protein 74 (WDR74), which consists of the WD repetition sequence, has been previously associated with tumor tumorigenesis. However, its mechanism of action in CRC remains unclear. Here, we found that WDR74 expression was upregulated in CRC tissues and cells. Downregulation of WDR74 repressed the proliferation and cell cycles in CRC cells. In addition, WDR74 knockdown induced cell apoptosis and suppressed both cell metastasis and invasion. Mechanistically, WDR74 decreased the phosphorylation of β-catenin and induced nuclear β-catenin accumulation, activating the Wnt/β-catenin signaling pathway in CRC cells. Further investigation showed that blocking the Wnt/β-catenin signaling pathway by XAV-939 reversed the effects of WDR74 on cell proliferation, migration, and invasion in HCT116 cells. Overall, WDR74 induced β-catenin translocation to the nucleus and activated the Wnt/β-Catenin, thus facilitated CRC cell proliferation and metastasis. In summary, WDR74 could be a potential target for the intervention of CRC.

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Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

10.21203/rs.2.12980/v1 ◽

2019 ◽

Author(s):

Deyu LIU ◽

xinchun jian ◽

PU XU ◽

Rong ZHU ◽

Yuan WANG

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Clinical Importance ◽

Migration And Invasion ◽

Lymphnode Metastasis ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

Abstract Background Mounting studies demonstrate long non-coding RNAs (lncRNAs) play an important role in tumor progression. However, the potential biological functions and clinical importance of linc01234 in oral squamous cell carcinoma (OSCC) still remain unclear. Methods Two OSCC cells were transfected with siRNAs targeting linc01234, and RT-qPCR, CCK-8, EDU, wound healing and Transwell and western blot assays were performed to analyze the effect of linc01234 on cell proliferation, migration and invasion. Bioinformatic analysis, luciferase assays and RT-qPCR identified a competitive endogenous RNAs (ceRNAs) among linc01234, miR-433-3p and PAK4. Results We found that linc01234 was significantly upregulated in OSCC tissues and cell lines and positively associated with T stage, lymphnode metastasis, differentiation. Kaplan-Meier analysis of OSCC reveals a positive correlation between linc01234 and the overall survival. Following the linc01234 deletion, the cell proliferation and metastasis abilities in CAL27 and SCC25 cells were found to be extremely reduced. Mechanism studies indicated that linc01234 located in cytoplasm and shared microRNA (miRNA) response elements with miR-433-3p. Luciferase assays indicated that miR-433-3p bind to the 3′-UTR of PAK4. Conclusions Our results indicated that linc01234 functioned as an oncogene in OSCC and might be a potential therapeutic target for OSCC.

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Hsa_circ_0026416 promotes proliferation and migration in colorectal cancer via miR-346/NFIB axis

Cancer Cell International ◽

10.1186/s12935-020-01593-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yahang Liang ◽

Jingbo Shi ◽

Qingsi He ◽

Guorui Sun ◽

Lei Gao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Molecular Mechanisms ◽

Xenograft Model ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Potential Biomarker ◽

Mouse Xenograft Model

Abstract Background Colorectal cancer (CRC) is one of the most common cancers worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been confirmed to be key regulators of many diseases. With many scholars devoted to studying the biological function and mechanism of circRNAs, their mysterious veil is gradually being revealed. In our research, we explored a new circRNA, hsa_circ_0026416, which was identified as upregulated in CRC with the largest fold change (logFC = 3.70) of the evaluated circRNAs via analysing expression profiling data by high throughput sequencing of members of the GEO dataset (GSE77661) to explore the molecular mechanisms of CRC. Methods qRT-PCR and western blot analysis were utilized to assess the expression of hsa_circ_0026416, miR-346 and Nuclear Factor I/B (NFIB). CCK-8 and transwell assays were utilized to examine cell proliferation, migration and invasion in vitro, respectively. A luciferase reporter assay was used to verify the combination of hsa_circ_0026416, miR-346 and NFIB. A nude mouse xenograft model was also utilized to determine the role of hsa_circ_0026416 in CRC cell growth in vivo. Results Hsa_circ_0026416 was markedly upregulated in CRC patient tissues and plasma and was a poor prognosis in CRC patients. In addition, the area under the curve (AUC) of hsa_circ_0026416 (0.767) was greater than the AUC of CEA (0.670), CA19-9 (0.592) and CA72-4 (0.575). Functionally, hsa_circ_0026416 promotes cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, hsa_circ_0026416 may function as a ceRNA via competitively absorbing miR-346 to upregulate the expression of NFIB. Conclusions In summary, our findings demonstrate that hsa_circ_0026416 is an oncogene in CRC. Hsa_circ_0026416 promotes the progression of CRC via the miR-346/NFIB axis and may represent a potential biomarker for diagnosis and therapy in CRC.

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