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

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.

scholarly journals FUT8-AS1 Inhibits the Malignancy of Melanoma Through Promoting miR-145-5p Biogenesis and Suppressing NRAS/MAPK Signaling

2021 ◽  
Vol 10 ◽  
Author(s):  
Xiang-jun Chen ◽  
Sha Liu ◽  
Dong-mei Han ◽  
De-zhi Han ◽  
Wei-jing Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Melanoma Cell ◽  
Ectopic Expression ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Functional Assays ◽  
Skin Malignancy ◽  
Melanoma Cell Proliferation ◽  
Signaling Axis

Melanoma is the major lethal skin malignancy. However, the critical molecular drivers governing melanoma progression and prognosis are still not clear. By analyzing The Cancer Genome Atlas (TCGA) data, we identified FUT8-AS1 as a prognosis-related long non-coding RNA (lncRNA) in melanoma. We further confirmed that FUT8-AS1 is downregulated in melanoma. Reduced expression of FUT8-AS1 is correlated with aggressive clinical factors and inferior overall survival. Using in vitro functional assays, our findings demonstrated that ectopic expression of FUT8-AS1 represses melanoma cell proliferation, migration, and invasion. FUT8-AS1 silencing promotes melanoma cell proliferation, migration, and invasion. Furthermore, in vivo functional assays demonstrated that FUT8-AS1 represses melanoma growth and metastasis. Mechanistically, FUT8-AS1 was found to bind NF90, repress the interaction between NF90 and primary miR-145 (pri-miR-145), relieve the repressive roles of NF90 on mature miR-145-5p biogenesis, and thus promote miR-145-5p biogenesis and upregulate mature miR-145-5p level. The expression of FUT8-AS1 is positively correlated with miR-145-5p in melanoma tissues. Via upregulating miR-145-5p, FUT8-AS1 reduces the expression of NRAS, a target of miR-145-5. FUT8-AS1 further represses MAPK signaling via downregulating NRAS. Functional rescue assays demonstrated that inhibition of miR-145-5p reverses the tumor suppressive roles of FUT8-AS1 in melanoma. The oncogenic roles of FUT8-AS1 silencing are also blocked by MAPK signaling inhibitor MEK162. In conclusion, these findings demonstrate that FUT8-AS1 exerts tumor suppressive roles in melanoma via regulating NF90/miR-145-5p/NRAS/MAPK signaling axis. Targeting FUT8-AS1 and its downstream molecular signaling axis represent promising therapeutic strategies for melanoma.

scholarly journals Long noncoding RNA HEIH promotes melanoma cell proliferation, migration and invasion via inhibition of miR-200b/a/429

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Haiying Zhao ◽  
Guoping Xing ◽  
Yingying Wang ◽  
Zengxiang Luo ◽  
Guoyan Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Melanoma Cell ◽  
Noncoding Rna ◽  
Prognostic Biomarker ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Transcriptional Inhibition ◽  
Melanoma Cell Proliferation ◽  
Melanoma Patients ◽  
Poor Outcomes

Long noncoding RNAs (lncRNAs) are frequently dysregulated and have important roles in many diseases, particularly cancers. lncRNA-HEIH was first identified in hepatocellular carcinoma (HCC). The expression, clinical significance and roles of lncRNA-HEIH in melanoma are still unknown. In the present study, we found that lncRNA-HEIH is highly expressed in melanoma tissues and cell lines, associated with advanced clinical stages, and predicts poor outcomes in melanoma patients. Functional assays showed that ectopic expression of lncRNA-HEIH promotes melanoma cell proliferation, migration and invasion. Knockdown of lncRNA-HEIH inhibits melanoma cell proliferation, migration and invasion. Mechanistically, we revealed that lncRNA-HEIH directly binds to miR-200b/a/429 promoter and represses miR-200b/a/429 transcription. The expression of miR-200b is inversely associated with lncRNA-HEIH in melanoma tissues. Furthermore, overexpression of miR-200b/a/429 abrogates melanoma cell proliferation, migration and invasion enhanced by lncRNA-HEIH. In conclusion, we identified lncRNA-HEIH as a key oncogene in melanoma via transcriptional inhibition of miR-200b/a/429. Our data suggested that lncRNA-HEIH may serve as a promising prognostic biomarker and therapeutic target for melanoma.

scholarly journals Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Mélissa Labelle-Côté ◽  
Julie Dusseault ◽  
Salma Ismaïl ◽  
Aude Picard-Cloutier ◽  
Peter M Siegel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Melanoma Cell ◽  
Primary Melanoma ◽  
Human Melanoma ◽  
Human Melanoma Cell ◽  
Migration And Invasion ◽  
Melanoma Cell Proliferation

lncRNA NEAT1 facilitates melanoma cell proliferation, migration, and invasion via regulating miR‐495‐3p and E2F3

2019 ◽  
Vol 234 (11) ◽  
pp. 19592-19601 ◽  
Author(s):  
Ying Xia ◽  
Yu Zhou ◽  
Han Han ◽  
Peng Li ◽  
Wei Wei ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Melanoma Cell ◽  
Migration And Invasion ◽  
Melanoma Cell Proliferation ◽  
Lncrna Neat1

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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yanli Zhang ◽  
Jianbing Hou ◽  
Shaomin Shi ◽  
Juan Du ◽  
Yudong Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Potential Biomarker ◽  
Melanoma Cell Proliferation ◽  
Tumorigenesis And Progression ◽  
Proliferation And Metastasis ◽  
Melanoma Patients ◽  
Cell Proliferation And Metastasis

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.

RNA m 6 A methylation regulates uveal melanoma cell proliferation, migration, and invasion by targeting c‐Met

2020 ◽  
Vol 235 (10) ◽  
pp. 7107-7119 ◽  
Author(s):  
Guangying Luo ◽  
Weiwei Xu ◽  
Yunping Zhao ◽  
Shanshan Jin ◽  
Siqi Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Uveal Melanoma ◽  
Melanoma Cell ◽  
Migration And Invasion ◽  
Uveal Melanoma Cell ◽  
Melanoma Cell Proliferation

scholarly journals Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Xiangjun Chen ◽  
Sha Liu ◽  
Xiaochun Zhao ◽  
Xiao Ma ◽  
Guozhen Gao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Skin Cancer ◽  
Melanoma Cell ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Prognostic Biomarker ◽  
Migration And Invasion ◽  
Melanoma Cell Proliferation ◽  
Malignant Skin ◽  
Melanoma Patients

Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.

scholarly journals IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis

2020 ◽  
Vol 11 (9) ◽  
pp. 2679-2687 ◽  
Author(s):  
Yuanmin He ◽  
Yan Yang ◽  
Jixiang Xu ◽  
Yongmei Liao ◽  
Li Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Melanoma Cell ◽  
Cutaneous Melanoma ◽  
Migration And Invasion ◽  
Melanoma Cell Proliferation

Inhibition of Migration and Invasion of Hepatocarcinoma HepG2 Cells by Dietary Saponins via Targeting HIF-1α

2018 ◽  
Vol 18 (7) ◽  
pp. 1025-1031
Author(s):  
Cheng Luo ◽  
Di Wu ◽  
Meiling Chen ◽  
Wenhua Miao ◽  
Changfeng Xue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Confocal Microscopy ◽  
Protein Expression ◽  
Mtt Assay ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Rt Pcr ◽  
Gene And Protein Expression ◽  
Simulated Hypoxia

Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined. Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy. Results： ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation. Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly

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