Long Non-coding RNAs as Regulators of the Mitogen-activated Protein Kinase (MAPK) Pathway in Cancer

Tasharrofi, Behnoosh; Ghafouri‐Fard, Soudeh

doi:10.14735/amko201895

Cited by 33 publications

(23 citation statements)

References 55 publications

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“…Notably, the present study demonstrated that lncRNA GATA6-AS, which has an important regulatory role in the growth of endothelial cells (10), may also participates in the metastasis of cervical squamous cell carcinoma. It was determined that the role of GATA6-AS in cervical squamous cell It has been reported that lncRNAs serve key roles in normal physiological processes and pathological changes (15).…”

Section: Discussionsupporting

confidence: 50%

“…As a key member of the mitogen-activated protein kinase signaling pathway, mitogen-activated protein kinase kinase 4 (MTK-1) participates in critical cell developmental processes and functions (9). It has been demonstrated that long non-coding RNAs (lncRNAs), a subgroup of non-coding RNAs composed of >200 nucleotides, are critical regulators of mitogen-activated protein kinase in cancer development (10). GATA binding protein 6 antisense (GATA6-AS) is a recently identified lncRNA that is involved in the regulation of the growth of endothelial cells (11); however, to the best of our knowledge, the involvement of GATA6-AS in other physiological or pathological processes remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

et al. 2019

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The diagnosis and treatment of cervical squamous cell carcinoma is challenged by difficulties in the determination of tumor invasion. GATA binding protein 6 antisense (GATA6-AS) is a recently identified long non-coding RNA that exhibits critical functions in the growth of endothelial cells; however, to the best of our knowledge, its involvement in other physiological and pathological processes is unknown. By reverse transcription-quantitative polymerase chain reaction, the present study examined the expression of GATA6-AS in tumor tissues and adjacent healthy tissues, and the serum from patients with cervical squamous cell carcinoma and healthy controls. The diagnostic and prognostic potentials of GATA6-AS for cervical squamous cell carcinoma were analyzed by receiver operating characteristic curve analysis and survival curve analysis, respectively. Associations between the serum levels of GATA6-AS and clinical characteristics of patients with cervical squamous cell carcinoma were analyzed by a χ 2 test. A GATA6-AS overexpression vector was transfected into cervical squamous cell carcinoma cells, and the effects on cell migration and invasion were investigated by Transwell migration and invasion assays, respectively. The expression of mitogen-activated protein kinase kinase 4 (MTK-1) following transfection with the GATA6-AS overexpression vector was detected by western blot analysis. It was identified that the expression levels of GATA6-AS were lower in tumor tissues compared with healthy tissues. In addition, serum levels of GATA6-AS were higher in patients compared with healthy controls. The serum levels of GATA6-AS were associated with tumor metastasis, and may serve as a potential diagnostic and prognostic marker for cervical squamous cell carcinoma. Furthermore, GATA6-AS overexpression inhibited cancer cell migration and invasion. The expression levels of MTK-1 were also reduced following GATA6-AS overexpression. Therefore, the present study proposed that downregulated GATA6-AS expression was associated with tumor metastasis in cervical squamous cell carcinoma, and that GATA6-AS expression may inhibit cancer cell migration and invasion by downregulating MTK-1.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

et al. 2019

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“…Genomewide association studies have recently mapped a large proportion of disease‐ or trait‐associated single nucleotide polymorphisms outside the protein coding regions of the genome, often in or near genes transcribed into lncRNAs (Bartonicek et al, ; Gong, Liu, Zhang, Miao, & Guo, ). There are bona fide examples of lncRNA linked to one or multiple hallmarks of cancer in a variety of cancers, including melanoma, in which many emerge as regulators of the MAPK and PI3K pathways (for review, Huang et al, ; Leucci, Coe, Marine, & Vance, ; Schmitt & Chang, ; Tasharrofi & Ghafouri‐Fard, ).…”

Section: Introductionmentioning

confidence: 99%

“…There are bona fide examples of lncRNA linked to one or multiple hallmarks of cancer in a variety of cancers, including melanoma, in which many emerge as regulators of the MAPK and PI3K pathways (for review, Huang et al, 2018;Leucci, Coe, Marine, & Vance, 2016;Schmitt & Chang, 2016;Tasharrofi & Ghafouri-Fard, 2018).…”

Section: Introductionmentioning

confidence: 99%

The lncRNA RMEL3 protects immortalized cells from serum withdrawal‐induced growth arrest and promotes melanoma cell proliferation and tumor growth

Cardoso

Serafim

Kawakami

et al. 2018

Pigment Cell Melanoma Res

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RMEL3 is a recently identified lncRNA associated with BRAFV600E mutation and melanoma cell survival. Here, we demonstrate strong and moderate RMEL3 upregulation in BRAF and NRAS mutant melanoma cells, respectively, compared to melanocytes. High expression is also more frequent in cutaneous than in acral/mucosal melanomas, and analysis of an ICGC melanoma dataset showed that mutations in RMEL3 locus are preponderantly C > T substitutions at dipyrimidine sites including CC > TT, typical of UV signature. RMEL3 mutation does not correlate with RMEL3 levels, but does with poor patient survival, in TCGA melanoma dataset. Accordingly, RMEL3 lncRNA levels were significantly reduced in BRAFV600E melanoma cells upon treatment with BRAF or MEK inhibitors, supporting the notion that BRAFMEK- ERK pathway plays a role to activate RMEL3 gene transcription. RMEL3 overexpression, in immortalized fibroblasts and melanoma cells, increased proliferation and survival under serum starvation, clonogenic ability, and xenografted melanoma tumor growth. Although future studies will be needed to elucidate the mechanistic activities of RMEL3, our data demonstrate that its overexpression bypasses the need of mitogen activation to sustain proliferation/survival of non-transformed cells and suggest an oncogenic role for RMEL3.

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“…We further verified the combined effect of MALAT1 and miR-503 on NPC proliferation, apoptosis, and ECM degradation, as well as the involvement of the MAPK pathway. Upon IL-1β stimulation, MALAT1 overexpression remarkably enhanced the NPC proliferation and NPC number ( Previous studies have shown that MALAT1 can affect the MAPK/AP1 signaling pathway [19], which is an important pathway for IVD [15]. Therefore, we examined the relationship between MALAT1, miR-503 and the MAPK pathway.…”

Section: Malat1 Inhibits Mir-503 To Regulate the Function Of Npcs Andmentioning

confidence: 99%

LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503

Zheng

Wang

et al. 2020

Preprint

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Background: Intervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects. Results: We validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro, overexpressed MALAT1 could attenuate the effect of IL-1β on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo, MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment. Conclusion: Our data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.

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Long Non-coding RNAs as Regulators of the Mitogen-activated Protein Kinase (MAPK) Pathway in Cancer

Cited by 33 publications

References 55 publications

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

Upregulation of lncRNA GATA6‑AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK‑1

The lncRNA RMEL3 protects immortalized cells from serum withdrawal‐induced growth arrest and promotes melanoma cell proliferation and tumor growth

LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503

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