Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Qiu, Junjun; Lin, Yingying; Ding, Jianxun; Feng, Weiwei; Jin, Huajun; Hua, Keqin

doi:10.3892/ijo.2015.2943

Cited by 122 publications

(110 citation statements)

References 32 publications

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“…ANRIL depletion has been associated with reduced proliferation (28), suggesting a procarcinogenic role supported by overexpression of this lncRNA in various others cancer types (29)(30)(31). In our IBC series, ANRIL overexpression was observed more particularly in the aggressive TNC subtype.…”

Section: Discussionmentioning

confidence: 58%

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

Meseure

Vacher

Alsibai

et al. 2016

Molecular Cancer Research

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ANRIL, a long noncoding RNA (lncRNA), has recently been reported to have a direct role in recruiting polycomb repressive complexes PRC2 and PRC1 to regulate the expression of the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster. Expression analysis of ANRIL, EZH2, SUZ12, EED, JARID2, CBX7, BMI1, p16, p15, and p14/ARF genes was evaluated in a large cohort of invasive breast carcinomas (IBC, n ¼ 456) by qRT-PCR and immunohistochemistry (IHC) was performed on CBX7, EZH2, p14, p15, p16, H3K27me3, and H3K27ac. We observed significant overexpression in IBCs of ANRIL (19.7%) and EZH2 (77.0%) and an underexpression of CBX7 (39.7%). Correlations were identified between these genes, their expression patterns, and several classical clinical and pathologic parameters, molecular subtypes, and patient outcomes, as well as with proliferation, epithelial-mesenchymal transition, and breast cancer stem cell markers. Multivariate analysis revealed that combined EZH2/ CBX7 status is an independent prognostic factor (P ¼ 0.001). In addition, several miRNAs negatively associated with CBX7 underexpression and EZH2 overexpression. These data demonstrate a complex pattern of interactions between lncRNA ANRIL, several miRNAs, PRC2/PRC1 subunits, and p15/CDKN2B-p16/CDKN2A-p14/ARF locus and suggest that their expression should be considered together to evaluate antitumoral drugs, in particular the BET bromodomain inhibitors.Implications: This study suggests that the global pattern of expression rather than expression of individual family members should be taken into account when defining functionality of repressive Polycomb complexes and therapeutic targeting potential.

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Section: Discussionmentioning

confidence: 58%

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

Meseure

Vacher

Alsibai

et al. 2016

Molecular Cancer Research

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“…Increasing evidence indicates that eukaryotic genomes and transcriptomes are the precursors for a number of non-coding RNAs (22), in addition to their established roles as protein-coding genes. Studies have highlighted key regulatory roles of lncRNAs in carcinogenesis and have suggested that some lncRNAs may be potential diagnostic and therapeutic targets in the treatment of OC (23,24).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA MALAT1 is upregulated and involved in cell proliferation, migration and apoptosis in ovarian cancer

Wang

Guo

2017

Experimental and Therapeutic Medicine

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Abstract. Ovarian cancer (OC) is the leading cause of mortality among gynecological malignancies. Although microRNAs are known to have a key regulatory role in OC, the involvement of long non-coding RNAs in the disease is less established. Previous studies have demonstrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a tumor oncogene in many cancers, though its role in OC remains unclear. The present study reported that MALAT1 expression was markedly upregulated in OC, by knockdown of MALAT1 expression in vivo, using RNA interference (RNAi) with small-interfering RNA (siRNA). It was found that MALAT1 expression was positively correlated with the International Federation of Gynecology and Obstetrics stages of OC, tumor histological grade and lymph node metastasis. In addition, the differential MALAT1 levels between a human ovarian epithelial cell line (HOSE) and OC cell lines (ES-2, OVCAR3, SKOV3 and HO8910) were compared in vitro. Notably, MALAT1 was expressed to a high level in OC cells. Furthermore, exogenous knockdown of MALAT1 significantly repressed growth and migration of OC cells, and promoted their apoptosis. Collectively, the current findings suggest that upregulation of MALAT1 in OC may facilitate tumorigenesis and metastasis. Knockdown of MALAT1 expression has potential as a novel target for the diagnosis and therapy of OC.

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“…Moreover, lncRNAs are considered to be dysregulated in gastric,13, 14 colon,12 renal,15 breast16 and ovarian carcinomas 6. Several lncRNAs have been reported to be involved in the initiation and progression of ovarian cancer 17, 18, 19. Therefore, the exploration of the association between ncRNAs and ovarian cancer would be of great value.…”

Section: Introductionmentioning

confidence: 99%

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

Wang

Ning

Wei

et al. 2018

J Cellular Molecular Medi

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Ovarian cancer is the leading malignancy of the female reproductive system and is associated with inconspicuous early invasion and metastasis. We have previously reported that the oncogene OTUB1 plays a crucial role in ovarian cancer progression, but the role of its isoform, the non‐coding RNA OTUB1‐isoform2, in ovarian cancer is still elusive. Here, we reported that OTUB1‐isoform2 expression in ovarian cancer tissues was significantly higher than that in the paired paratumorous tissues (P < .01). The patients with high expression of OTUB1‐isoform2 had larger tumours than those with low expression (P < .05). The high expression of OTUB1‐isoform2 was correlated with the involvement of bilateral ovaries (P < .05), lymph node metastasis (P < .05), vascular invasion (P < .05), greater omentum involvement (P < .01), fallopian tube involvement (P < .05), advanced FIGO stages (P < .01) and recurrence (P < .01). Moreover, OTUB1‐isoform2 served as an independent negative prognostic predictor for disease‐free survival (DFS) and disease‐specific survival (DSS). Overexpression of OTUB1‐isoform2 in the ovarian cancer cells stimulated cell proliferation, migration and invasion both in vitro and in vivo. In summary, our study suggested that OTUB1‐isoform2 is a novel prognostic biomarker with independent oncogenic functions for ovarian cancer.

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Long non-coding RNA ANRIL predicts poor prognosis and promotes invasion/metastasis in serous ovarian cancer

Cited by 122 publications

References 32 publications

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

Long non-coding RNA MALAT1 is upregulated and involved in cell proliferation, migration and apoptosis in ovarian cancer

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

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