Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer

Xu, Tongpeng; Wang, Wenyu; Ma, Pei; Shuai, You; Zhao, Kun; Wang, Yanfen; Li, Wei; Xia, Rui; Chen, Wen-Ming; Zhang, Erbao; Shu, Yongqian

doi:10.1038/s41388-018-0308-y

Cited by 110 publications

(110 citation statements)

References 42 publications

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“…In the present study, lncRNA HCG11 was shown to be downregulated in glioma tissues and cells. According to previous reports, lncRNAs are associated with the prognosis of cancer patients . In the present study, we analyzed the prognostic potential of HCG11 in glioma.…”

Section: Discussionmentioning

confidence: 90%

Long non‐coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR‐4425/MTA3 axis

Zhang

Cao

Kou

et al. 2019

The Journal of Gene Medicine

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Background Glioma is a type of malignant tumor that occurs in the central nervous system of adults. Long non‐coding RNAs (lncRNAs) that potentially participate in the initiation and progression of glioma have been widely reported. As a now‐found lncRNA, HLA complex group 11 (HCG11) has not yet been studied in glioma. The present study aimed to determine the role of HCG11 in the tumorigenesis of glioma. Methods A quantitative real‐time polymerase chain reaction assay was performed to examine the expression pattern of HCG11 in 84 glioma tissues and cell lines. The overall survival rate of glioma patients with a high or low level of HCG11 or metastasis‐associated 1 family member 3 (MTA3) was analyzed by Kaplan–Meier analysis. The effect of HCG11 on glioma cell growth was determined by in vitro and in vivo experiments. MicroRNAs (miRNAs) that potentially interact with HCG11 were searched and determined by bioinformatics analysis and a luciferase reporter assay. Similarly, the target of miRNA‐4425 was identified. Finally, rescue assays were conducted to determine the bio‐function of the competing endogenous RNA pathway. Results HCG11 was downregulated in 84 pairs of glioma tissues and cell lines. Moreover, a low level of HCG11 indicted the lower overall survival rate of glioma patients. Regarding the mechanism, HCG11 was abundant in the cytoplasm of glioma cells and interacted with miR‐4425 to release the expression of MTA3. miR‐4425 and MTA3 participated in HCG11‐mediated glioma growth. Conclusions LncRNA HCG11 suppresses the growth of glioma by cooperating with the miR‐4425/MTA3 axis.

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Section: Discussionmentioning

confidence: 90%

Long non‐coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR‐4425/MTA3 axis

Zhang

Cao

Kou

et al. 2019

The Journal of Gene Medicine

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“…Recent years, FOXD2-AS1 has been suggested to be overexpressed in many types of human malignancy. Similarly, Xu et al 14 indicated that FOXD2-AS1 overexpression was positively associated with tumor size, invasion depth, lymphatic metastasis, distant metastasis, and TNM stage in gastric cancer patients. Interestingly, we analyzed TCGA database which includes 460 cutaneous melanoma tissue samples and 558 normal skin tissue samples and found levels of FOXD2-AS1 expression was significantly increased in cutaneous melanoma tissues compared with normal skin tissues.…”

Section: Discussionmentioning

confidence: 84%

“…Besides, high levels of FOXD2-AS1 expression were also found in digestive system neoplasms including gastric cancer, 13,14 colorectal cancer, 15,16 and esophageal squamous cell carcinoma. Recent years, FOXD2-AS1 has been suggested to be overexpressed in many types of human malignancy.…”

Section: Discussionmentioning

confidence: 99%

FOXD2‐AS1 correlates with the malignant status and regulates cell proliferation, migration, and invasion in cutaneous melanoma

Ren¹,

Zhu

Wu³

2018

J of Cellular Biochemistry

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Long noncoding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2‐AS1) has been shown to be dysregulated in several types of human cancer. However, the role of FOXD2‐AS1 in cutaneous melanoma was still unclear. In our study, FOXD2‐AS1 expression has been found to be upregulated in cutaneous melanoma tissue specimens and cell lines compared with that in normal tissue specimens and normal human epidermal melanocyte, respectively. Furthermore, high expression of FOXD2‐AS1 was obviously correlated with deep Breslow thickness, present ulceration, high Clark level and distant metastasis in cutaneous melanoma patients. However, there were no statistical associations between FOXD2‐AS1 expression and cutaneous melanoma patients’ disease‐free survival and overall survival. The results of loss‐of‐function study showed that inhibition of FOXD2‐AS1 suppresses cutaneous melanoma cell proliferation, migration and invasion through regulating phospho‐Akt expression. In conclusion, FOXD2‐AS1 is associated with clinical progression in cutaneous melanoma patients, and functions as oncogenic lncRNA in cutaneous melanoma cells.

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“…Of note, our results showed that nearly 20% of PGM5‐AS1 was located in the nucleus. Recent studies confirm that about one third of nuclear lncRNAs can physically interact with the PRC2 complex to epigenetically regulate gene expression, such as HOTAIR, SOX2‐OT, FOXD2‐AS1, and so on. Whether nuclear PGM5‐AS1 is able to regulate the expression of genes including PTEN through this mechanism needs further study.…”

Section: Discussionmentioning

confidence: 99%

p53‐induced long non‐coding RNA PGM5‐AS1 inhibits the progression of esophageal squamous cell carcinoma through regulating miR‐466/PTEN axis

et al. 2019

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A growing body of evidence suggests that long non‐coding RNA (lncRNA) is aberrantly expressed in human cancer and linked to cancer initiation and development. We previously identified Homo sapiens PGM5 antisense RNA 1 (PGM5‐AS1) as a novel esophageal squamous cell carcinoma (ESCC)‐related lncRNA by performing high‐throughput RNA sequencing. However, its clinical implication and biological function in ESCC are still uncharacterized. In the present study, we found that PGM5‐AS1 was frequently downregulated in ESCC tissues, plasma, and cell lines, and low PGM5‐AS1 expression was positively correlated with poor differentiation, advanced tumor node metastasis (TNM) stage, and lymph node metastasis. Importantly, PGM5‐AS1 was identified to be an effective diagnostic and prognostic biomarker for ESCC patients. Functional experiments revealed that exogenous expression of PGM5‐AS1 significantly suppressed the proliferation, migration, and invasion of ESCC cells in vitro as well as tumor growth in vivo. Mechanistically, PGM5‐AS1 was transcriptionally activated by p53 and it could directly interact with and sequester miR‐466 to elevate PTEN expression, thereby inhibiting ESCC progression. Overall, our data indicate that PGM5‐AS1 is a novel tumor suppressor in ESCC and restoration of PGM5‐AS1 may be a promising avenue for treatment of ESCC patient.

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Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer

Cited by 110 publications

References 42 publications

Long non‐coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR‐4425/MTA3 axis

Long non‐coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR‐4425/MTA3 axis

FOXD2‐AS1 correlates with the malignant status and regulates cell proliferation, migration, and invasion in cutaneous melanoma

p53‐induced long non‐coding RNA PGM5‐AS1 inhibits the progression of esophageal squamous cell carcinoma through regulating miR‐466/PTEN axis

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