HOXA10‑AS: A novel oncogenic long non‑coding RNA in glioma

Dong, Chengya; Cui, Jiayue; Li, Dian‐He; Li, Qi; Hong, Xinyu

doi:10.3892/or.2018.6662

Cited by 23 publications

(28 citation statements)

References 47 publications

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“…Transcriptional inhibition of HOXA10-AS and the resulting reduction in cell proliferation was robustly observed in experiments conducted with either of the two targeting siRNAs. These findings indicate the function of HOXA10-AS in regulating cell proliferation in glioma and confirm a recent report on this lncRNA [55].…”

Section: Resultssupporting

confidence: 92%

Comprehensive analysis of lncRNAs reveals candidate prognostic biomarkers in multiple cancer types

Isaev

Jiang

Lee

et al. 2019

Preprint

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12Long non-coding RNAs (lncRNAs) are increasingly recognized as functional units in can-13 cer pathways and powerful molecular biomarkers, however most lncRNAs remain un-14 characterized. Here we performed a systematic discovery of prognostic lncRNAs in 9,326 15 patient tumors of 29 types using a proportional-hazards elastic net machine-learning 16 framework. lncRNAs showed highly tissue-specific transcript abundance patterns. We 17 identified 179 prognostic lncRNAs whose abundance correlated with patient risk and im-18 proved the performance of common clinical variables and molecular tumor subtypes. 19 Pathway analysis revealed a large diversity of the high-risk tumors stratified by lncRNAs 20and suggested their functional associations. In lower-grade gliomas, discrete activation 21 of HOXA10-AS indicated poor patient prognosis, neurodevelopmental pathway activation 22 and a transcriptomic similarity to glioblastomas. HOXA10-AS knockdown in patient-de-23 rived glioblastoma cells caused decreased cell proliferation and deregulation of glioma 24 driver genes and proliferation pathways. Our study underlines the pan-cancer potential 25 of the non-coding transcriptome for developing molecular biomarkers and innovative 26 therapeutic strategies. 27 28 cancer patient prognosis with transcript abundance of protein-coding genes and their genetic 61 and epigenetic alterations [22][23][24][25]. However, associations of lncRNAs with cancer patient sur-62 vival and biological function remain largely unexplored. A recent study characterized recurrent 63 hypomethylation patterns affecting a thousand lncRNAs in the TCGA PanCanAtlas cohort and 64 identified the EPIC1 lncRNA as a marker of poor prognosis in a subset of breast cancers [26]. 65Another TCGA study associated mutations and transcript abundance profiles of lncRNAs with 66 regulatory networks and molecular pathways and nominated candidate oncogenic and tumor 67 suppressive lncRNAs, some of which were functionally validated in cancer cell lines [27]. Analy-68 sis of cell-cycle correlated lncRNAs revealed a subset of S-phase enriched lncRNAs whose 69 transcript abundance profiles correlated with patient survival in multiple TCGA cohorts [28]. 70However, those studies did not analyze robust prognostic performance of lncRNAs using ma-71 chine-learning and cross-validation approaches, indicating further potential to systematically dis-72 cover lncRNAs as candidate prognostic biomarkers of multiple cancer types. 73Here we evaluated the transcript abundance profiles of nearly 6,000 lncRNAs as prognostic bi-74 omarkers in human cancers. Using a comprehensive machine-learning analysis, we compiled a 75 robust catalogue of prognostic lncRNAs across nearly 10,000 tumors of 29 types from the 76 TCGA PanCanAtlas project [22, 29]. The majority of our candidate lncRNAs showed improved 77 prognostic potential compared to standard clinical features and molecular tumor subtypes. We 78 associated prognostic lncRNAs with large-scale deregulation of hallmark cancer pathways, re-79 vealing e...

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Section: Resultssupporting

confidence: 92%

Comprehensive analysis of lncRNAs reveals candidate prognostic biomarkers in multiple cancer types

Isaev

Jiang

Lee

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…LncRNAs execute critical modulators in many physiological and pathological processes, including embryonic pluripotency, developmental transitions, differentiation and epigenetic programs of the transcriptome [22,23]. In addition, lncRNAs may also play important roles in driving tumor suppression or in exerting oncogenic functions in a wide variety of cancer types, by promoting tumor cell proliferation, migration, invasion and metastasis [24,37]. Recently, a lncRNA named LincHOXA10, which resides at HOXA10 promoter and coordinates the activation of multiple 5′HOXA genes, has been identi ed as one of 231 lncRNAs associated with the human HOX loci [24].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, lncRNAs may also play important roles in driving tumor suppression or in exerting oncogenic functions in a wide variety of cancer types, by promoting tumor cell proliferation, migration, invasion and metastasis [24,37]. Recently, a lncRNA named LincHOXA10, which resides at HOXA10 promoter and coordinates the activation of multiple 5′HOXA genes, has been identi ed as one of 231 lncRNAs associated with the human HOX loci [24]. Furthermore, expression of LincHOXA10 has been identi ed as a negative prognostic factor in glioma patients [24].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a lncRNA named LincHOXA10, which resides at HOXA10 promoter and coordinates the activation of multiple 5′HOXA genes, has been identi ed as one of 231 lncRNAs associated with the human HOX loci [24]. Furthermore, expression of LincHOXA10 has been identi ed as a negative prognostic factor in glioma patients [24]. However, the functional role of LincHOXA10 in CRC remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…A novel lncRNA, LincHOXA10, is transcribed from the antisense strand of HOXA10 gene locus at chromosome 7p15.3. The knockdown of LincHOXA10 expression was shown to induce glioma cell apoptosis [24]. Shao et al found that LincHOXA10 drives liver tumor initiating cells (TICs) self-renewal and tumorigenesis [11].…”

Section: Introductionmentioning

confidence: 99%

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LincHOXA10 Facilitates Colorectal Cancer Development By Regulating HOXA10-Mediated Epithelial-Mesenchymal Transtion

Zhu

Zhang

et al. 2020

Preprint

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Background: Long non-coding RNAs (lncRNAs) have been reported to play an important role in tumorigenesis and metastasis of human colorectal cancer (CRC). However, the specific role of LincHOXA10 in CRC remains unknown.Methods: The expression of LincHOXA10 and HOXA10 in CRC cells and tissue samples was measured by quantitative reverse transcription PCR (qRT-PCR). The protein expression of HOXA10, E-cadherin, N-cadherin, Vinmentin, p-smad2 and p-smad3 was assessed by Western blotting or immunofluorescence staining. Cell proliferation, migration, and invasion were assessed by the MTT and transwell assays. Tumor growth in vivo was carried out by subcutaneous tumor formation in nude mice.Results: In the present study, we found that LincHOXA10 expression was significantly higher in human CRC tissues than the paired normal tissues. In fact, LincHOXA10 level correlated with the CRC tumor sizes and lymphatic metastasis. In cultured CRC cells, knockdown of LincHOXA10 inhibited cell proliferation, migration and invasion. LincHOXA10 deficiency also attenuated CRC tumor growth in vivo. Mechanistically, LincHOXA10 interacted with HOXA10 and regulated its expression. HOXA10 levels were interrelated to the LincHOXA10 level in CRC cells. Functionally, HOXA10 was essential for TGF-β1/SMADs-induced epithelial -mesenchymal transition of CRC cells, and HOXA10 played a critical role in mediating the function of LincHOXA10. Importantly, HOXA10 expression was significantly up-regulated in human CRC tissues.Conclusions: LincHOXA10 facilitates CRC development and metastasis via regulating HOXA10-mediated epithelial-mesenchymal transition of CRC cells.

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Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway

et al. 2020

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Glioma, a common malignant tumour of the human central nervous system, has poor prognosis and limited treatment options. Dissecting the biological mechanisms underlying glioma pathogenesis can facilitate the development of better therapies. Here, we investigated the endogenous expression of BTB and CNC homolog 2 (BACH2), fused in sarcoma (FUS), TSLNC8 and microRNA (miR)-10b-5p in glioma cells and tissues. We studied the interaction between BACH2 and FUS and its contribution to glioma progression. We demonstrated that the interaction between BACH2 and FUS promoted glioma progression via transcriptional inhibition of TSLNC8. Overexpression of TSLNC8 restrained glioma progression by suppressing miR-10b-5p. Binding of TSLNC8 to miR-10b-5p attenuated the suppression of WWC family member 3 (WWC3) by miR-10b-5p and activated the Hippo signalling pathway. Growth of subcutaneous xenografts could be inhibited by knockdown of BACH2 or FUS, by overexpressing TSLNC8 or a combination of the three, also leading to a prolonged survival in nude mice. Our results indicate that the BACH2 and FUS/TSLNC8/miR-10b-5p/WWC3 axis is responsible for glioma development and could serve as a potential target for the development of new glioma therapies.

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HOXA10‑AS: A novel oncogenic long non‑coding RNA in glioma

Cited by 23 publications

References 47 publications

Comprehensive analysis of lncRNAs reveals candidate prognostic biomarkers in multiple cancer types

Comprehensive analysis of lncRNAs reveals candidate prognostic biomarkers in multiple cancer types

LincHOXA10 Facilitates Colorectal Cancer Development By Regulating HOXA10-Mediated Epithelial-Mesenchymal Transtion

Interaction of BACH2 with FUS promotes malignant progression of glioma cells via the TSLNC8–miR‐10b‐5p–WWC3 pathway

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