Background: Ovarian cancer is the most fatal tumor of female's reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified suitable biomarkers to facilitate the early detection, prognosis evaluation, and the assessment of treatment response. However, the aim of this review was to investigate the role of long non-coding RNAs (lncRNAs) in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers. Methods: We performed an online literature search of the MEDLINE/PubMed databases using the key words ovarian cancer, lncRNA, and biomarker. Results: We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients' survival, metastasis potential as well as treatment response. Conclusions: Expression profiling as well as methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response.

Hypoxia-inducible factors (HIFs) have been shown to be upregulated in tumor tissues and linked with tumor progression and metastasis in breast cancer. Among regulatory mechanisms for HIF expression is a natural occurring antisense named aHIF, which has been shown to be overexpressed in breast cancer and influence the level of the HIF-1α transcript. In the present study, we analyzed the expression of HIF-1α and aHIF in breast cancer tissues versus adjacent noncancer tissues (ANCTs) in relation with the clinical and biological behavior of the tumors. aHIF has been shown to be expressed in 67.4% of invasive ductal carcinoma samples, while none of ANCTs showed its expression. HIF-1α has been expressed in all of tumors and 90% of ANCTs. Comparison of HIF-1α expression level between tumor and ANCT tissues showed a total upregulation in tumor samples. No statistically significant association has been found between the level of HIF-1α expression in tumor samples and clinicopathologic and demographic characteristics such as age, tumor size, estrogen receptor status, progesterone receptor status, HER2/neu expression level, lymph node status, histological grade, and stage except for a weak correlation between HIF-1α expression and Ki-67 status. Besides, we could not detect any significant correlation between relative expression of HIF-1α and aHIF in tumor samples. Collectively, these data suggest that aHIF overexpression can be used as a potential biomarker in breast cancer. However, further studies are needed for the evaluation of its mechanism of action in regulation of HIF-1α expression in different pathological conditions. HIF-1α overexpression results in the upregulation of several genes that participated in cancer-associated pathways such as proliferation, angiogenesis, and glucose metabolism. We showed that HIF-1α is upregulated in breast tumor samples compared with adjacent noncancerous tissues. Its expression has been associated with Ki-67 status. Its natural occurring antisense is only expressed in tumor tissues. Thus, it can be used as a potential biomarker in breast cancer.

Considering the role of this pathway in the pathogenesis of several cancers, alterations in lncRNA expression lead to changes in MAPK pathway resulting in inhibition of apoptosis and induction of cell proliferation and migration. Moreover, some lncRNAs participate in cross-talk between MAPK and other cancer-related pathways, such as PI3K/Akt pathway through regulation of certain shared proteins between these pathways. Based on the availability of certain anticancer drugs that modulate this pathway, identification of lncRNAs that affect this pathway would help in establishment of effective therapies.Key words: RNA - long noncoding - mitogen-activated protein kinases - signal transduction.

Background:Colon cancer-associated transcript 2 (CCAT2) is a newly recognized lncRNA transcribed from the 8q24 genomic region. It functions as an oncogene in various types of cancers including breast cancer, in which it affects Wnt/β-catenin pathway. Previous studies have shown a putative interaction between this lncRNA and MYC proto-oncogene.Methods:In the current study, we evaluated the expression of CCAT2 in breast cancer tissues with regards to the expression of its target MYC. In addition, we assessed the relationship between CCAT2 and MYC expression levels in tumor tissues and the clinical prognostic characteristics of breast cancer patients.Results:MYC expression levels were significantly up-regulated in tumor tissues compared with adjacent non-cancerous tissues (ANCTs), while such analysis showed no statistically significant difference between these two tissue types in CCAT2 expression. Starkly increased CCAT2 gene expression levels were found in 12/48 (25%) of cancer tissue samples compared with their corresponding ANCTs. Furthermore, significant inverse correlations were found between CCAT2 expression and stage, as well as lymph node involvement. Besides, a significant inverse correlation was found between the relative MYC expression in tumor tissues compared with their corresponding ANCTs and disease stage.Conclusions:These results highlight the significance of MYC and CCAT2 expressions in the early stages of breast cancer development and suggest a potentially significant role for CCAT2 in a subset of breast cancer patients, which could be applied as a potential therapeutic target in these patients.

Collectively, out data show downregulation of lncRNA-ATB in a significant number of breast tumor tissues compared with ANCTs and imply that lncRNA-ATB might have distinct roles in the pathogenesis of different cancers or even different subtypes of a certain cancer which should be evaluated in future studies.