SP1-activated long noncoding RNA lncRNA GCMA functions as a competing endogenous RNA to promote tumor metastasis by sponging miR-124 and miR-34a in gastric cancer

Tian, Yaru; Ma, Ran-Ran; Sun, Yujing; Liu, Haiting; Zhang, Hui; Sun, Yiyuan; Liu, Lei; Li, Yuhong; Song, Lin; Gao, Peng

doi:10.1038/s41388-020-1330-4

Cited by 47 publications

(42 citation statements)

References 38 publications

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“…Recent studies have shown that lncRNA dysregulation is involved in various malignancies, such as lung cancer 4 , esophageal cancer 5 , gastric cancer 6 , liver cancer 7 and PC 8 , 9 , by affecting diverse tumor biological behaviors, such as proliferation, invasion, migration and metastasis, both in vitro and in vivo. Increasing numbers of lncRNA studies in PC have been reported 9 - 12 .…”

Section: Introductionmentioning

confidence: 99%

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Liu¹,

Zheng²,

Zhang³

et al. 2020

Theranostics

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Background: Due to the limitations of strategies for its early diagnosis and treatment, pancreatic cancer (PC) remains a substantial human health threat. We previously discovered a methylation-mediated lncRNA, LINC00261, which is downregulated in PC tissues. However, the underlying role of LINC00261 in PC remains largely unknown. Methods: Quantitative real-time PCR and in situ hybridization were performed to evaluate the expression levels of LINC00261 in PC, adjacent nontumor and normal pancreas tissues. The clinical significance of LINC00261 was assessed in multicenter PC samples. The functions of LINC00261 in PC were investigated by gain- and loss-of-function assays in vitro and in vivo . Potential downstream pathways and mechanisms were explored via RNA sequencing and bioinformatic analyses. RNA immunoprecipitation and chromatin immunoprecipitation assays were used to validate the underlying mechanisms. Pyrosequencing and targeted demethylation of the LINC00261 promoter were performed to explore the upstream epigenetic mechanisms and therapeutic potential. Results: LINC00261 was significantly downregulated in PC tissues, and its expression was positively associated with the prognosis of PC patients. Phenotypic studies indicated that LINC00261 overexpression significantly suppressed PC cell proliferation, migration and metastasis in vitro and in vivo . c-Myc was identified as a downstream target of LINC00261. LINC00261 repressed c-Myc transcription by physically interacting and binding with the bromo domain of p300/CBP, preventing the recruitment of p300/CBP to the promoter region of c-Myc and decreasing the H3K27Ac level. Moreover, the methylation level of the LINC00261 promoter was high in PC tissues and was correlated with poor prognosis. Targeted demethylation of the LINC00261 promoter inhibited PC progression both in vitro and in vivo . Conclusions: Our findings indicate that methylation-mediated LINC00261 suppresses PC progression by epigenetically repressing c-Myc expression. These findings expand the therapeutic potential of LINC00261, possibly providing evidence to support the development of epigenetic drugs or therapeutic strategies. This research adds further insights into the etiology of PC and indicates that LINC00261 may be a prognostic and therapeutic target in PC.

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Section: Introductionmentioning

confidence: 99%

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Liu¹,

Zheng²,

Zhang³

et al. 2020

Theranostics

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“…The mechanism of action of lncRNA is extremely complicated and has not yet been fully understood, among which the well-verified one is that lncRNA can act as a miRNA molecular sponge and regulate the expression of miRNA targets (Thomson and Dinger, 2016). For example, lnc-GCMA activated by SP1 competitively sponged miR-124 and miR-34a to increase slug and snail expression, thus promoting gastric cancer metastasis in vitro and in vivo (Tian et al, 2020). LINC00173.v1 increased VEGFA level via sponging miR-511-5p, facilitating angiogenesis and progression of lung squamous cell carcinoma (Chen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p

Cao

Yang²,

et al. 2020

Front. Genet.

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Emerging evidence suggests that long non-coding RNA (lncRNA) plays a critical role in human disease progression. Recently, a novel lncRNA ST8SIA6-AS1 was shown as an important driver in various cancer types. Nevertheless, its contribution to lung adenocarcinoma (LUAD) remains undocumented. Herein, we found that ST8SIA6-AS1 was frequently overexpressed in LUAD cell lines, tissues, and plasma. Depletion of ST8SIA6-AS1 significantly inhibited LUAD cell proliferation and invasion in vitro and tumor growth in vivo. In term of mechanism, ST8SIA6-AS1 was transcriptionally repressed by tumor suppressor p53, and ST8SIA6-AS1 was mainly located in the cytoplasm and could abundantly sponge miR-125a-3p to increase nicotinamide N-methyltransferase (NNMT) expression, thereby facilitating LUAD malignant progression. Clinically, high ST8SIA6-AS1 was positively correlated with larger tumor size, lymph node metastasis, and later TNM stage. Moreover, ST8SIA6-AS1 was identified as an excellent indicator for MM diagnosis and prognosis. Collectively, our data demonstrate that ST8SIA6-AS1 is a carcinogenic lncRNA in LUAD, and targeting the axis of ST8SIA6-AS1/miR-125a-3p/NNMT may be a promising treatment for LUAD patients.

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“…Plenty of researches have indicated that transcription factors could bring about the aberrant expressions of lncRNAs in various carcinomas. Emerging documents indicated that SP1 plays the role of transcription factor in a serious of cancers, such as gastric cancer and cervical cancer (16)(17)(18). Therefore, we speculated whether SP1 could interact with lncRNA NCK1-AS1 promoter in BC cells.…”

Section: Transcription Factor Sp1 Targets Nck1-as1 Promoter Regionmentioning

confidence: 94%

Sp1-activated Long Noncoding RNA NCK1-AS1 Facilitates Cell Growth of Breast Cancer via Sponging miR-361-5p 

Jia

Zhang

et al. 2020

Preprint

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Background: Breast cancer (BC) is one of the most lethal and malignant tumors in the world. Accumulating documents have illuminated the vital roles of long noncoding RNAs (lncRNAs) which are closely related to the progression of human cancers, including BC. LncRNA NCK1-AS1 was reported to be an oncogene in some cancers; nevertheless, its functionality is not well elucidated in BC. Methods: NCK1-AS1 expression status was detected in human breast cancer tissues and cell lines by the means of RT-qPCR. The impacts of NCK1-AS1 deficiency on breast cancer cell stemness, viability, proliferation, migration, invasion, and apoptosis were measured in vitro via sphere formation assay, western blot analysis, CCK-8, colony formation, transwell, TUNEL and flow cytometry analysis. Furthermore, luciferase reporter assay, RIP and ChIP were used to verify the mutual effects between molecules.Results: In this study, lncRNA NCK1-AS1 was verified to be elevated in BC tissues and cells. In addition, NCK1-AS1 silencing hampered BC cell growth by inhibiting cell stemness, viability, proliferation, migration and invasion as well as promoting cell apoptosis. Moreover, NCK1-AS1 functioned as a molecular sponge for miR-361-5p and modulated SP1 expression. Rescue experiments signified that SP1 overexpression restored NCK1-AS1 silencing-mediated suppression on BC cell growth. Importantly, SP1 was uncovered to bind with NCK1-AS1 promoter, suggesting a positive feedback loop of NCK1-AS1/miR-361-5p/SP1 in BC cells. Conclusion: Taken together, these findings showed for the first time that NCK1-AS1 served as a carcinogenic gene in BC cells via combining with miR-361-5p to upregulate SP1.

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SP1-activated long noncoding RNA lncRNA GCMA functions as a competing endogenous RNA to promote tumor metastasis by sponging miR-124 and miR-34a in gastric cancer

Cited by 47 publications

References 38 publications

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p

Sp1-activated Long Noncoding RNA NCK1-AS1 Facilitates Cell Growth of Breast Cancer via Sponging miR-361-5p

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SP1-activated long noncoding RNA lncRNA GCMA functions as a competing endogenous RNA to promote tumor metastasis by sponging miR-124 and miR-34a in gastric cancer

Cited by 47 publications

References 38 publications

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription

Long Non-coding RNA ST8SIA6-AS1 Promotes Lung Adenocarcinoma Progression Through Sponging miR-125a-3p

Sp1-activated Long Noncoding RNA NCK1-AS1&nbsp;Facilitates Cell Growth of Breast Cancer via Sponging miR-361-5p&nbsp;

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Sp1-activated Long Noncoding RNA NCK1-AS1 Facilitates Cell Growth of Breast Cancer via Sponging miR-361-5p