Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway

Yu, Li; Xiong, Fang; Yang, Liting; Bo, Hao; Gong, Zhaojian; Wang, Yumin; Fang, Wei; Tang, Yue; Li, Xiayu; Liao, Qianjin; Wang, Hui; Zhou, Ming; Xiang, Bo; Wu, Xu; Yong, Li; Li, Xiaoling; Chen, Xiang; Li, Guiyuan; Guo, Can; Zeng, Zhaoyang; Xiong, Wei

doi:10.1186/s13046-018-0918-9

Cited by 147 publications

(110 citation statements)

References 73 publications

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“…However, in recent years, various functions of lncRNAs have been identified, including participating in the autophagy pathway 2,3 , controlling cell differentiation 4 , and acting as competing endogenous RNAs (ceRNAs) for microRNAs 2,5 . The role of some lncRNAs as ceRNAs of miRNAs has been demonstrated in cancer metastasis and invasion [6][7][8][9] . For example, Lian et al reported that lncRNA AFAP1-AS1 acted as a ceRNA of miR-432-5p, to promote metastasis in nasopharyngeal carcinoma.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3′-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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“…One such recognized is lncRNA ZEB1-AS1, which epigenetically activates ZEB1 and promotes prostate cancer metastasis [33]. Previously, lncRNA AFAP1-AS1 was reported to act as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis [34]; while Yin et al demonstrated that AFAP1-AS1 is associated with poor survival of patients with non-small cell lung cancer, and enhances cell proliferation via inhibition of p21 expression [35]. Until now, the exact regulatory mechanism of AFAP1-AS1 in cancer progression and resistance is not defined.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

Han¹,

Gu²,

Lü³

et al. 2020

Mol Cancer

150

126

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Background: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.Methods: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain-or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.Results: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.Conclusion: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

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“…Malignant tumors are a major threat to human health. Nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer are common malignant tumors that show high rates of metastasis . Moreover, the malignant progression and high mortality rates associated with these tumors are related to their insidious onset, frequent metastasis and recurrence, and poor prognosis .…”

Section: Discussionmentioning

confidence: 99%

“…Nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer are common malignant tumors that show high rates of metastasis. [26][27][28] Moreover, the malignant progression and high mortality rates associated with these tumors are related F I G U R E 2 circMAN1A2 was highly expressed in the sera of patients with oral cancer, thyroid cancer, ovarian cancer, or lung cancer. A-D, Relative expression of circMAN1A2 in oral cancer (A), thyroid cancer (B), ovarian cancer (C), and lung cancer (D).…”

Section: Discussionmentioning

confidence: 99%

circMAN1A2 could serve as a novel serum biomarker for malignant tumors

et al. 2019

Self Cite

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Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real‐time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.

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Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway

Cited by 147 publications

References 73 publications

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation

circMAN1A2 could serve as a novel serum biomarker for malignant tumors

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