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

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.

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

Bioscience Reports ◽

10.1042/bsr20170682 ◽

2017 ◽

Vol 37 (3) ◽

Cited By ~ 29

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.

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MicroRNA‐23a inhibits melanoma cell proliferation, migration, and invasion in mice through a negative feedback regulation of sdcbp and the MAPK/ERK signaling pathway

IUBMB Life ◽

10.1002/iub.1979 ◽

2018 ◽

Vol 71 (5) ◽

pp. 587-600 ◽

Cited By ~ 2

Author(s):

Shelian Lu ◽

Qunyuan Xu

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Melanoma Cell ◽

Negative Feedback ◽

Feedback Regulation ◽

Erk Signaling ◽

Migration And Invasion ◽

Negative Feedback Regulation ◽

Melanoma Cell Proliferation

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

BMC Cancer ◽

10.1186/1471-2407-11-443 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 22

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

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

Journal of Cellular Physiology ◽

10.1002/jcp.28559 ◽

2019 ◽

Vol 234 (11) ◽

pp. 19592-19601 ◽

Cited By ~ 15

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

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

Journal of Cellular Physiology ◽

10.1002/jcp.29608 ◽

2020 ◽

Vol 235 (10) ◽

pp. 7107-7119 ◽

Cited By ~ 5

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

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

Bioscience Reports ◽

10.1042/bsr20171031 ◽

2017 ◽

Vol 37 (6) ◽

Cited By ~ 25

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.

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