Long non-coding RNAs in hematologic malignancies: road to translational research

Hajjari, Mohammadreza; Khoshnevisan, Atefeh; Shin, Young Kee

doi:10.3389/fgene.2013.00250

Cited by 11 publications

(9 citation statements)

References 8 publications

(10 reference statements)

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“…LncRNAs are ncRNA transcripts longer than 200 nucleotides (nt) that are transcribed from various genomic locations, such as in the promoters, enhancers, introns, or antisense coding regions of genes, or in their own stand-alone position in the genome [18]. Based on their roles, the dysregulation of lncRNAs is involved in several diseases including cancer [19,20]. In the present study, we examined the expression of LncRNA HOTTIP and its clinicopathological/ prognostic significance in 86 specimens of primary TSCCs and 14 samples of adjacent non-malignant samples.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

et al. 2015

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Long non-coding RNAs (lncRNAs) have been demonstrated to be a critical role in cancer progression and prognosis. However, little is known about the pathological role of lncRNA HOXA transcript at the distal tip (HOTTIP) in tongue squamous cell carcinoma (TSCC) patients. The aim of this study is to measure the expression of lncRNA HOTTIP in TSCC patients and to explore the clinical significance of the lncRNA HOTTIP. The expression of lncRNA HOTTIP was measured in 86 TSCC tissues and 14 adjacent non-malignant tissues using qRT-PCR. In our study, results indicated that lncRNA HOTTIP was highly expressed in TSCC compared with adjacent non-malignant tissues (P < 0.001) and positively correlated with T stage (T1-2 vs. T3-4, P = 0.023), clinical stage (I-II stages vs. III-IV stages, P = 0.018), and distant metastasis (absent vs. present, P = 0.031) in TSCC patients. Furthermore, we also found that lncRNA HOTTIP overexpression was an unfavorable prognostic factor in TSCC patients (P < 0.001), regardless of T stage, distant metastasis, and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for TSCC patients through multivariate analysis (P = 0.023). In conclusion, increased lncRNA HOTTIP expression may be serve as an unfavorable prognosis predictor for TSCC patients. Nevertheless, further investigation with a larger sample size is needed to support our results.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

et al. 2015

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“… 2 , 3 Long non-coding RNAs (lncRNAs), defined as transcripts longer than 200 nucleotides, 4 affect various cellular functions such as gene regulation, genomic imprinting, RNA maturation and translation. 5 , 6 Moreover, multiple lines of evidence link dysregulation of lncRNAs to diverse human diseases, especially cancer. In the process of carcinogenesis, certain lncRNAs have been attributed to oncogenic and/or tumor suppressor roles.…”

Section: Introductionmentioning

confidence: 99%

Dysfunction of the WT1-MEG3 signaling promotes AML leukemogenesis via p53-dependent and -independent pathways

et al. 2017

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Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA maternally expressed gene 3 (MEG3) inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly downregulated in AML and suppresses leukemogenesis not only in a p53-dependent, but also a p53-independent manner. In addition, MEG3 is proven to be transcriptionally activated by Wilms’ tumor 1 (WT1), dysregulation of which by epigenetic silencing or mutations is causally involved in AML. Therefore MEG3 is identified as a novel target of the WT1 molecule. Ten–eleven translocation-2 (TET2) mutations frequently occur in AML and significantly promote leukemogenesis of this disorder. In our study, TET2, acting as a cofactor of WT1, increases MEG3 expression. Taken together, our work demonstrates that TET2 dysregulated WT1-MEG3 axis significantly promotes AML leukemogenesis, paving a new avenue for diagnosis and treatment of AML patients.

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“…10,11 Dysregulation of lncRNAs is associated with various types of malignancies. [12][13][14] LncRNAs can regulate both oncogenic and tumor-suppressive pathways. 15 A number of lncRNAs have been described to be involved in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial–mesenchymal transition

Cui

2017

Tumour Biol.

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Long non-coding RNAs play important roles in the regulation of cellular processes including cell proliferation, differentiation, and metastasis. The dysregulation of long non-coding RNAs, such as the SPRY4-IT1 (SPRY4 intronic transcript 1), has been associated with various types of malignancies. However, the functional roles and regulatory mechanism of SPRY4-IT1 in ovarian cancer remain to be elucidated. Here, we quantified the expression level of SPRY4-IT1 in ovarian cancer patients and found its downregulation in ovarian cancer tissues compared to the adjacent normal tissues. Patients with lower SPRY4-IT1 expression were associated with a relatively poor prognosis. In consistency, the expression of SPRY4-IT1 was found to be reduced in four human ovarian cancer cell lines compared to normal ovarian epithelial cells. Next, two ovarian cancer cell lines SKOV3 and HO8910 were employed in vitro assays to investigate biological functions of SPRY4-IT1 in ovarian cancer. The cell proliferation was reduced following SPRY4-IT1 overexpression in SKOV3/HO8910 cells based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. The SPRY4-IT1 overexpression also dramatically arrested cell cycle and promoted cell apoptosis. Both wound-healing and transwell-based assays demonstrated that cell migration and invasion were inhibited following SPRY4-IT1 overexpression. Meanwhile, overexpression of SPRY4-IT1 increased E-cadherin and decreased N-cadherin and vimentin protein levels, indicating that SPRY4-IT1 may regulate ovarian cancer cell metastasis through the inhibition of epithelial-mesenchymal transition. Taken together, our findings suggest that SPRY4-IT1 regulates various cellular processes of ovarian cancer cells and its downregulation may contribute to ovarian cancer progression and metastasis partly via affecting the epithelial-mesenchymal transition.

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Long non-coding RNAs in hematologic malignancies: road to translational research

Cited by 11 publications

References 8 publications

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

Dysfunction of the WT1-MEG3 signaling promotes AML leukemogenesis via p53-dependent and -independent pathways

Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial–mesenchymal transition

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