Competing endogenous RNA network crosstalk reveals novel molecular markers in colorectal cancer

Samir, Nehal; Matboli, Marwa; El-Tayeb, Hanaa; El-Tawdi, Ahmed Hassan Fawzi; Hassan, Mohmed K.; Waly, Amr A.; Ramadan, Mohamed G.; Al‐Belkini, Tarek N.; El‐Khamisy, Sherif F.; El-Asmar, Farid

doi:10.1002/jcb.26884

Cited by 12 publications

(7 citation statements)

References 38 publications

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“…In our previous study, HOXA11-AS was found to function as a competing endogenous RNA (ceRNA) to regulate peptidyl arginine deiminase 2 expression by sponging miR-125a-5p, promoting the metastasis of CRC [15]. It was reported that some lncRNAs may be related to several miRNAs in ceRNA regulation of CRC [16]. In our previous study, many associated miRNAs including miR-149-3p were found to potentially participate in the function of HOXA11-AS as a ceRNA regulator of CRC metastasis.…”

Section: Ivyspringmentioning

confidence: 99%

The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer

et al. 2020

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Background: Metastasis is the primary cause of death in colorectal cancer (CRC); the underlying mechanisms remain partly unknown. In this study, we aim to investigate the value of HOXA11-AS in survival evaluation and the potential role of HOXA11-AS/miR-149-3p axis in the CRC metastasis. Methods: The expressions of HOXA11-AS, both in obtained CRC samples and adjacent noncancerous tissues, were analyzed in survival evaluation. Competing endogenous RNAs (CeRNAs) Analysis were employed to reveal the potential relationship between HOXA11-AS and miR-149-3p. It was further confirmed by Quantitative real-time polymerase chain reaction (qRT-PCR) and Dual-luciferase reporter assay. Migration and invasion assay were used to verify the potential role of HOXA11-AS and miR-149-3p in the regulation of CRC metastasis. The potential pathway was explored by Western blot analysis. Results: The expression of HOXA11-AS in the CRC tissue is significantly higher than the expression in adjacent noncancerous tissue (p<0.0001). High expressions of HOXA11-AS were noticeably correlated with clinicopathologic characteristics including advanced clinical stage (p=0.021), larger tumor size (p<0.001) and frequent tumor recurrence (p=0.001). The overall survival in HOXA11-AS-High group was significantly shorter than the HOXA11-AS-Low group (p<0.001). Advanced clinical stage, tumor size and high expression of HOXA11-AS were showed as independent prognostic prediction factors for the 5-year tumor relapse of CRC patients (p<0.001). HOXA11-AS acts as a potential molecular sponge for miR-149-3p, in the promotion of CRC metastasis. In the miR-149-3p mimic-treated group, the expression of E-cadherin was increased, whereas the expression of N-cadherin, Snail, Slug, TGF-β1, Wnt2b, Twist and C/EBPβ was decreased. Conclusion: This study demonstrates that high expression of HOXA11-AS is correlated with CRC progression and poor prognosis and may promote metastasis via EMT by modulating miR-149-3p.

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Section: Ivyspringmentioning

confidence: 99%

The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer

et al. 2020

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“…The expression levels of LncRNAs were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Seven types of lncRNAs were recognized as tumor promoters [10,11,13,14,[21][22][23][24][25] and six were tumor suppressors [7,9,[26][27][28][29] in CRC patients. The associations between lncRNAs and clinicopathologic parameters in CRC patients are shown in Table 1.…”

Section: Study Parameters and Study Qualitymentioning

confidence: 99%

Clinical diagnostic value of long non-coding RNAs in Colorectal Cancer: A systematic review and meta-analysis

Bi¹,

Zhang²,

Fan³

et al. 2020

J. Cancer

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Background: Histopathological diagnosis remains the gold standard for the diagnosis of cancer, including colorectal cancer, but it is infeasible when tumor tissue is not available. With the recognition of long non-coding RNAs (lncRNAs), the expression of lncRNAs in serum or tissue samples has been reported as a diagnosis method for some cancers, however, the diagnostic value of lncRNAs for colorectal cancer remains unclear. Methods: A systematic review and meta-analysis were conducted. Eligible studies were identified through a comprehensive literature search in PubMed, PubMed Central, Web of Science, Embase, and Cochrane Library (up to May 05, 2020) according to the selection criteria. Meta-DiSc, Review Manager and STATA were used to analyze the association between lncRNAs expression and the diagnosis of colorectal cancer. Results: Fifteen studies that analyzed the expression of 15 lncRNAs in 1434 CRC patients were included. The summary area under the curve (AUC) of lncRNA for the diagnosis efficacy between patients with and without CRC was estimated to be 0.8629, corresponding to a weighted sensitivity of 0.75 (95% CI: 0.72-0.77), specificity of 0.80 (95%CI: 0.78-0.82). Subgroup analysis illustrated that the AUC of blood-based detection of lncRNA showed 0.8820, pooled DOR: 18.57, while tissue-based analysis showed 0.8203, pooled DOR: 10.47. Blood-based tests were then divided into two categories, plasma-based and serum-based lncRNA testing. Results revealed that the AUC of serum-based detection was 0.9077, pooled DOR: 26.64, and plasma-based detection was 0.5000, pooled DOR: 11.80. Conclusions: This meta-analysis indicates that the aberrantly expressed lncRNAs might serve as potential diagnostic biomarkers for CRC patients and blood-based lncRNA analysis is of higher diagnostic accuracy than tissue-based testing. Moreover, serum-based lncRNA testing achieved higher diagnostic efficacy than plasma-based analysis.

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“…Otherwise, a growing body of evidence indicated that lncRNAs were combined with its target microRNAs (miRs) so that impeded the combination from miRs and the 3′-untranslated region (3′-UTR) of the target gene, thereby controlling the expression of the target gene and regulating cell function. [ 19 ] This kind of RNAs is known as competing endogenous RNAs (ceRNA). [ 20 ] For example, lncRNA DANCR promoted EMT, migration, and invasion of cholangiocarcinoma cells by transcriptionally activating Twist1 by sponging miR-345-5p.…”

Section: Introductionmentioning

confidence: 99%

LncRNA AFAP1-AS1/miR-27b-3p/VEGF-C axis modulates stemness characteristics in cervical cancer cells

Xia

Duan

et al. 2021

Chinese Medical Journal

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Background: Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC. Methods: Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C. Results: CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells. Conclusions: LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.

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Competing endogenous RNA network crosstalk reveals novel molecular markers in colorectal cancer

Cited by 12 publications

References 38 publications

The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer

The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer

Clinical diagnostic value of long non-coding RNAs in Colorectal Cancer: A systematic review and meta-analysis

LncRNA AFAP1-AS1/miR-27b-3p/VEGF-C axis modulates stemness characteristics in cervical cancer cells

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