Non-coding RNA ROR Research Articles

Retraction: The long non-coding RNA-ROR promotes osteosarcoma progression by targeting miR-206.

Dan Fei, Guoqing Sui, Yang Lu, Long Tan, Zhao Dongxu, Kewei Zhang. The long non-coding RNA-ROR promotes osteosarcoma progression by targeting miR-206. J Cell Mol Med. 2019; 23: 1865-1872. https://doi.org/10.1111/jcmm.14087. The above article, published online on 19 December 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, Stefan Constantinescu, The Foundation for Cellular and Molecular Medicine and John Wiley and Sons Ltd. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed inappropriate duplications of images between this and other articles that were previously published in a different scientific context. Thus, the editors consider the conclusions of this manuscript substantially compromised. Although the authors requested a retraction, when asked to approve the retraction wording, they remained unresponsive.

Functions of long non-coding RNA ROR in patient-derived glioblastoma cells

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer in adult patients. A variety of long non-coding RNAs play an important role in the pathogenesis of GBM, however the molecular functions of most of them still remain elusive. Here, we investigated linc-RoR (long intergenic non-protein coding RNA, regulator of reprogramming) using GBM neurospheres obtained from 12 different patients. We demonstrated that the highest level of this transcript is detected in cells with increased EGFR expression. According to our data, linc-RoR knockdown decreases cell proliferation, increases sensitivity to DNA damage, and downregulates the level of cancer stem cell (CSC) markers. On the other hand, linc-RoR overexpression promote cell growth and increases the proportion of CSCs. Analysis of RNA sequencing data revealed that linc-RoR affects expression of genes involved in the regulation of mitosis. In agreement with this observation, we have showen that the highest level of linc-RoR is detected in the G2/M phase of the cell cycle, when linc-RoR is localized on the chromosomes of dividing cells. Based on our results, we can propose that linc-RoR performs pro-oncogenic functions in human gliobalstoma cells, which may be associated with the regulation of mitotic progression and GBM stemness.

Long chain noncoding RNA-ROR promotes hypoxic injury of cardiomyocytes by targeting the miR-145/HAX-1 axis.

BackgroundLong non-coding RNAs (lncRNAs) are a class of non-protein coding RNAs greater than 200 nucleotides (nt) in length which have been shown to be significantly highly expressed in the heart tissue of mice undergoing thoracic aortic arch constriction (TAC). Micro RNAs (miRNAs) are a class of non-protein-coding RNAs. Many miRNAs have been reported to play a key role in the progression of myocardial hypertrophy. In this study, we aimed to investigate whether lncRNA reprogramming regulators (ROR) promotes hypoxic injury in cardiomyocytes by targeting and regulating the miR-145/HS1-associated protein X-1 (HAX-1) axis.MethodsA mouse model of myocardial hypertrophy was established by conventional TAC method, and the cardiomyocytes were isolated. We transfected pcDNA3.0-ROR vector, pcDNA3.0-HAX-1 vector plasmid, and miR-145 simulant into cardiomyocytes with Lipofectamine 2000. Luciferase reporter gene was used to analyze the targeting relationship between genes.ResultsThe expression of ROR in hypertrophic myocardium was significantly increased after phenylephrine (PE) intervention. After transfection with si-ROR, the ROR expression in hypertrophic cardiomyocytes treated with PE decreased significantly. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), creatine kinase (CK) decreased and superoxide dismutase (SOD) increased. The expression of miR-145 in cardiomyocytes was significantly down-regulated after PE treatment. In hypertrophic cardiomyocytes, after up-regulating the expression of miR-145, the relative messenger ribonucleic acid (mRNA) and protein expressions of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) induced by PE decreased. Compared with the miR-NC group, wild type (WT)-ROR activity in the miR-145 group was significantly inhibited (P<0.05), and mutant (MUT)-ROR activity had no significant change (P>0.05). When cardiomyocytes were transfected with HAX-1 3'URT WT vector along with miR-145 simulant, miR-145 inhibitor, and their respective controls. Compared with the control groups, the luciferase activity of cells transfected with simulant was significantly decreased (P<0.05), and increased in inhibitor group (P<0.05). Transfection of HAX-1 3'URT mutant vector did not show this phenomenon. ROR was negatively correlated with miR-145 expression and positively correlated with HAX-1 mRNA.ConclusionsThe lncRNA ROR can promote the expression of HAX-1 by competitive binding with miR-145, so as to promote the pathophysiological process of myocardial hypertrophy.

LncRNA ROR and miR-125b Predict the Prognosis in Heart Failure Combined Acute Renal Failure.

Objective To elucidate the correlation between expression levels of long noncoding RNA (lncRNA) ROR and microRNA-125b (miR-125b) with the prognosis in heart failure (HF) patients combined acute renal failure (ARF). Methods HF patients combined ARF (n = 90) and healthy controls (n = 90) in the same period were included in our hospital from April 2016 to December 2018. Every subject was followed up for 24 months. Serum levels of lncRNA ROR and miR-125b were detected, and their expression correlation was analyzed by Pearson correlation test. Receiver operating characteristic (ROC) curves were depicted for assessing the sensitivity and specificity of lncRNA ROR and miR-125b in diagnosing HF combined ARF. Results lncRNA ROR was upregulated in serum of HF patients combined ARF, and its level was positively correlated to NYHA classification. miR-125b displayed an opposite trend. In serum samples of HF combined ARF, expression level of lncRNA ROR was negatively related to that of miR-125b. Diagnostic potentials of lncRNA ROR and miR-125b in HF combined ARF were confirmed by ROC curve analyses (lncRNA ROR: AUC = 0.9199, cutoff value = 5.595, sensitivity = 92.22%, and specificity = 73.33%; miR-125b: AUC = 0.8509, cutoff value = 2.290, sensitivity = 81.11%, and specificity = 74.44%). After 2-year follow-up, 16 cases were dead. Higher incidences of death and rehospitalization were observed in HF combined ARF cases expressing higher serum level of lncRNA ROR or lower level of miR-125b. Conclusions Serum level of lncRNA ROR is upregulated, and miR-125b is downregulated in HF patients combined ARF. Their levels are linked to NYHA classification, which can be utilized as prognostic biomarkers in HF combined ARF.

Retraction.

Retraction: "Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway," by Peng-Wei Lu, Lin Li, Fang Wang, Yuan-Ting Gu, J Cell Physiol. 2019; 1904-1912: The above article, published online on 26 August 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.27066), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid.

Long non-coding RNA ROR recruits histone transmethylase MLL1 to up-regulate TIMP3 expression and promote breast cancer progression

BackgroundAs a significant cause of cancer deaths worldwide, breast cancer continues to be a troublesome malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the development of breast cancer. Abnormal methylation has been associated with unfavorable breast cancer prognosis. Herein, the current study aimed to elucidate the role of lncRNA ROR in breast cancer.MethodsRT-qPCR was performed to determine whether lncRNA ROR was highly expressed in breast cancer tissues, while lncRNA ROR expression was detected in both the nuclear and cytoplasm of breast cancer cells. MCF-7 cells were subsequently introduced with oe-lncRNA ROR, sh-lncRNA ROR to explore the effects of lncRNA ROR on cell proliferation, invasion and apoptosis.ResultsRIP, RNA pull-down and ChIP assays provided evidence suggesting that lncRNA ROR recruited transmethylase MLL1 to promote H3K4 trimethylation that enhanced TIMP3 transcription. The rescue experiments demonstrated that lncRNA ROR knockdown could inhibit the progression of breast cancer via the downregulation of TIMP3. Finally, the in vivo experiment findings consistently highlighted the suppressive effects of lncRNA ROR silencing on tumor growth.ConclusionTaken together, our study demonstrates that silencing of lncRNA ROR inhibits breast cancer progression via repression of transmethylase MLL1 and TIMP3, emphasizing the potential of lncRNA ROR as a novel target against breast cancer.

Экспрессия длинных некодирующих РНК ROR и MALAT1 при миоме матки

Objective. To study the expression level of long non-coding RNAs ROR and MALAT1 in tissue samples of uterine fibroids. Patients and methods. Samples of myomatous nodes and tissues of normal myometrium in 28 women of reproductive age were examined. The analysis of the expression of long non-coding RNAs was carried out using a real-time reverse-transcription polymerase chain reaction (RT-PCR) with specific primers. Results. There was a significant decrease in the expression level of long non-coding RNA ROR and an increase in the MALAT1 expression in tissue samples of uterine fibroids relative to the control group. Conclusion. The results obtained demonstrate a possible role of long non-coding RNAs in the development of uterine fibroids and correlate with the data which we obtained for patients with endometriosis. Detecting the expression level of long non-coding RNAs can improve the existing methods for diagnosing this disease. However, further research is required to determine the clinical significance of MALAT1 and ROR, and the molecular mechanisms underlying the action of these RNAs in uterine fibroid cells. Key words: long non-coding RNAs, uterine fibroids, myomectomy, lncROR, MALAT1

LncRNA-ROR/microRNA-185-3p/YAP1 axis exerts function in biological characteristics of osteosarcoma cells

AimThe co-expression network of long non-coding RNA ROR (lncRNA-ROR) and microRNA-185-3p (miR-185-3p) has not been focused on osteosarcoma. Therein, this work was initiated to uncover lncRNA-ROR and miR-185-3p functions in osteosarcoma. MethodsLncRNA-ROR, miR-185-3p and Yes-associated protein 1 (YAP1) expression in osteosarcoma tissues and cells were detected. The screened cells (MG63 and U2OS) were transfected with decreased and/or increased lncRNA-ROR and miR-185-3p to explore osteosarcoma progression. Tumor growth was detected by tumor xenografts in mice. ResultsUp-regulated lncRNA-ROR and YAP1 and down-regulated miR-185-3p were found in osteosarcoma. LncRNA ROR knockdown or miR-185-3p overexpression inhibited osteosarcoma cell progression while lncRNA ROR elevation or miR-185-3p inhibition presented the opposite effects. Function of lncRNA ROR was rescued by miR-185-3p and regulated the growth and metastasis of osteosarcoma cells via modulating YAP1, the target gene of miR-185-3p. ConclusionThis work illustrates that lncRNA-ROR down-regulation or miR-185-3p up-regulation inhibits osteosarcoma progression via YAP1 repression.

Long non-coding RNA ROR sponges miR-138 to aggravate hypoxia/reoxygenation-induced cardiomyocyte apoptosis via upregulating Mst1

BackgroundHypoxia/reoxygenation (H/R) injury of cardiomyocytes causes an irreversible damage to heart and largely results in acute myocardial infarction. Study has indicated lncRNA ROR aggravates myocardial ischemia/reperfusion (I/R) injury. Also, lncRNA ROR sponges miR-138 to promote osteogenesis. MiR-138 involves in hypoxic pulmonary vascular remodelling by targeting Mst1. However, the interaction between lncRNA ROR, miR-138 and Mst1 involved in myocardial H/R injury is still unknown. MethodsH9C2 cells were used to establish H/R injury model. The expression levels of lncRNA ROR and miR-138 were modified by transfection with the miR-138 mimics or lncRNA ROR overexpression plasmid. MTT and flow cytometry analysis were performed to detect cell proliferation and apoptosis. Dual luciferase reporter assay was used to determine interaction between lncRNA ROR and miR-138 or miR-138 and Mst1. Expression levels of lncRNA ROR, miR-138, Mst1 and apoptosis-related markers were determined by qRT-PCR or western blotting. ResultsLncRNA ROR was significantly up-regulated, while miR-138 was obviously down-regulated in H/R-induced injury of H9C2 cells. Furthermore, miR-138 overexpression alleviated cardiac cell apoptosis induced by H/R injury. Mst1 was revealed to be a target of miR-138 and negatively regulated by miR-138. Mst1 overexpression reversed the protective effects of miR-138 on H/R injury of H9C2 cells. LncRNA ROR was identified as a sponge for miR-138. MiR-138 could protect H9C2 cells form H/R injury induced by lncRNA ROR overexpression. ConclusionOur study provides that lncRNA ROR sponges miR-138 to aggravate H/R-induced myocardial cell injury by upregulating the expression of Mst1.

Long noncoding RNA ROR promotes proliferation and invasion of colorectal cancer by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p.

Colorectal cancer is one of the most common cancers in the world. LncRNA ROR, is a tumor oncogene associated with various human cancers. However, the role of ROR in colorectal cancer cells still remains unknown. The aim of this study was to measure the expression level of ROR and clarify its biological functions in colorectal cancer cells. The expression level of ROR in colorectal cancer cells was detected using qRT-PCR. We performed CCK8 assay, colony formation assay, cell migration and invasion assays to evaluate the effects of ROR on cell proliferation, migration and invasion of colorectal cancer cells. Then, transfection of ROR, ROR inhibitor, miRNA-223-3p-mimics and miRNA-223-3p-inhibitor, qRT-PCR, and luciferase reporter assay were used to explore the molecular mechanisms. In the present study, Lnc-ROR was highly expressed in colorectal cancers compared with adjacent non-cancerous normal tissues. And the expression level of ROR was also increased in colorectal cancer cells (p < 0.05). CCK8 assay and invasion assay suggested that ROR can promote cell proliferation and invasion. The luciferase reporter assay showed ROR acted as sponge and directly competed with miRNA-223-3p, then decreasing the expression of tumor suppressor gene NF2. The findings of this study first revealed that ROR was upregulated in colorectal cancer cells and can promote cell proliferation and invasion by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p.

The Long Non-Coding RNA-RoR Promotes the Tumorigenesis of Human Colorectal Cancer by Targeting miR-6833-3p Through SMC4.

BackgroundLong non-coding RNA regulator of reprogramming (LINC-RoR) has shown different expressions in a variety of tumors as a stem cell inducer through reprogramming regulation. However, its role and regulation mechanisms in colorectal cancer (CRC) are still unclear.Materials and MethodsQuantitative real-time PCR and Western blot were performed to examine LINC-RoR expression in paired CRC samples and cell lines. The relationship of LINC-RoR expression with clinicopathological characteristics and clinical outcomes was analyzed. The biological functions of LINC-RoR were studied by MTS and colony formation in vitro. Cell apoptosis was analysed by the flow cytometry. The Dual-luciferase reporter assays and RIP assays were performed to explore the regulatory relationship of LINC-RoR.ResultsIn this study, we found that LINC-RoR was upregulated in CRC cell lines and tissues. High expression of LINC-RoR was associated with poorer survival time and multivariate analysis results showed that LINC-RoR was an independent risk factor of tumor malignancy progression. Overexpression of LINC-RoR promoted the cell proliferation and knocked down it can reverse the effect in vitro. The regulatory network of LINC-ROR/miR-6833-3p/SMC4 was predicted with bioinformatics analysis tools and validated via dual-luciferase reporter assays and RIP. Further study revealed that in overexpression LINC-RoR cell lines the expression of miR-6833-3p was downregulated and miR-6833-3p can inhibit its target gene SMC4, the apoptosis-related protein.ConclusionWe concluded that LINC-RoR functions as an oncogene in CRC through the miR-6833-3p/SMC4 pathway.

Long non-coding RNA ROR confers arsenic trioxide resistance to HepG2 cells by inhibiting p53 expression

Arsenic trioxide is an effective drug in the treatment of hematologic malignancies, but it has no obvious therapeutic effect on liver cancer. Long non-coding RNA ROR is a newly found long-noncoding RNA that has been reported to get involved in the regulation of chemo-resistance in multiple cancers. However, whether and how long non-coding RNA ROR gets involved in the resistance to arsenic trioxide in liver cancer has not been explored. In this study, We found that cellular apoptosis was increased by arsenic trioxide in liver cancer HepG2 cells; P53 expression was also increased by arsenic trioxide at both mRNA level and protein level, indicating that P53-dependent apoptosis is the main mechanism for arsenic trioxide to induce cytotoxicity in liver cancer HepG2 cells. Meanwhile, we found an obvious increase in the level of long non-coding RNA ROR in arsenic trioxide-treated HepG2 cells. By measuring the level of reactive oxygen species, glutathione, superoxide dismutase, and malondialdehyde, the product of lipid peroxidation, we further demonstrated that oxidative stress was a potential factor for both the activation of P53 expression and the increase in long non-coding RNA ROR expression. Through the knock-down of long non-coding RNA ROR by siRNA, we revealed that the activated long non-coding RNA ROR ameliorated arsenic trioxide-induced apoptosis by inhibiting P53 expression. Together, our study reported that long non-coding RNA ROR conferred arsenic trioxide resistance to liver cancer cells through inhibiting P53 expression, and long non-coding RNA ROR might be a novel sensitizing target for liver cancer treatment.

Diagnostic Value of lncRNA ROR in Differentiating Ovarian Cancer Patients.

The current study aims to investigate the prognostic value of long non-coding RNA (lncRNA) ROR in ovarian cancer patients. Sixty cases of ovarian cancer patients were collected from January 2017 to December 2017. The expression of lncRNA ROR in the plasma and tissues of ovarian cancer was detected by RT-qPCR. The relationship between the expression of lncRNA ROR and the clinicopathological characteristics was analyzed. The expression of lncRNA ROR in the plasma of ovarian cancer patients was significantly higher than that in healthy controls. Compared with that in the adjacent non-cancerous tissues, the level of lncRNA ROR was significantly enhanced in the ovarian cancer tissues. Further study showed that the expression of lncRNA ROR was closely related to FIGO stage, tumor grade, and lymph node metastasis. Pearson's correlation assay indicated that lncRNA ROR positively correlated with CA125 in ovarian cancer patients. Moreover, the combined detection of plasma lncRNA ROR and CA125 had the highest value in the diagnosis of ovarian cancer compared to that of lncRNA ROR or CA125 alone. The enhanced level of plasma lncRNA ROR could be used as a potential biomarker for the diagnosis of ovarian cancer.

Long non-coding RNA ROR mitigates cobalt chloride-induced hypoxia injury through regulation of miR-145

Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is a condition causing apnea and hypopnea. LncRNA-ROR revealed properties in regulating hypoxia response. Our study explored the roles of ROR in CoCl2-induced hypoxia injury in HK-2 cells. HK-2 cells were treated with CoCl2 to induce hypoxia injury. Cell viability, cell apoptosis and apoptotic proteins were detected using CCK-8, flow cytometry and western blot, respectively. The alter expression of ROR and miR-145 was achieved through transfection. Moreover, the expressions of HIF-α and ERK and MAPK related factors were examined using western blot. We found that CoCl2 decreased cell viability and increased apoptosis as well as increased the expression of ROR. ROR overexpression increased cell viability, decreased cell apoptosis. ROR overexpression upregulated anti-apoptotic proteins Bcl-2 and decreased p53, Bax and cleaved-Caspase-3. ROR overexpression also increased the expression of HIF-α. On the opposite, ROR silence led to the opposite results as relative to ROR overexpression. ROR overexpression decreased expression of miR-145. Co-transfection with ROR overexpression and miR-145 impaired the promoting effects of ROR in CoCl2 treated cells. ROR increased phosphorylation of ERK while decreased phosphorylation of MAPK. In conclusion, lncRNA ROR alleviated CoCl2-induced hypoxia injury through regulation of miR-145 as well as modulating ERK and MAPK signalling. Highlights CoCl2 induces ROR upregulation; Overexpression of ROR reduces CoCl2-induced HK-2 cell injury; Silence of ROR promotes CoCl2-induced HK-2 cell injury; Overexpression of ROR decreases miR-145 expression; ROR overexpression modulates ERK and MAPK signalling pathways through regulation of miR-145.

Prognostic value of long noncoding RNA ROR in patients with cancer in China: A systematic review and meta-analysis.

Background:For cancer, it is common that there is usually a dysregulation of the long noncoding RNA regulator of reprogramming (LncRNA ROR). To illustrate the application of LncRNA ROR, which serves as the prognostic marker for the malignant tumors, it is of great importance to conduct a meta-analysis.Methods:There were 3 databases being applied. The data used were collected before January 5, 2018. These 3 databases include the OVID, PubMed, and Science databse. To further explore the association between the expression and survival of LncRNA ROR, it calculated the 95% confidence intervals (CIs) and hazard ratios (HRs). Meanwhile, the odds ratios (ORs) have been calculated for the evaluation of the correlation between the pathological and expression parameters of LncRNA ROR.Results:There were 8 researches participated by 720 patients. According to the HR, it has been implied that there was a high LncRNA ROR expression related with the weak disease-free survival (DFS) (HR = 3.48, 95% CI, 2.24–5.41) and overall survival (OS) (HR = 2.47, 95% CI, 1.76–3.47) among the cancer patients with none dramatic heterogeneity. There was also a correlation among lymph node metastasis (OR = 5.38, 95% CI, 2.21–13.12), high tumor stage (OR = 3.80, 95% CI, 1.95–7.41), and larger tumor size (OR = 4.43, 95% CI, 1.26–15.51).Conclusions:Thus, it can be predicted about the lymph node metastasis and high tumor stage, larger tumor size, DFS, and poor OS based on the high LncRNA ROR. This suggests that high LncRNA ROR can be used as a new indicator of poor prognosis in cancer.

Mechanism of LncRNA ROR promoting prostate cancer by regulating Akt.

To investigate the expression of long-chain non-coding RNA ROR in prostate cancer (PCa), and to further study its possible underlying mechanisms in prostate cancer. Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the level of lncRNA ROR in 42 pairs of PCa tissues and adjacent normal tissues, and the correlation between ROR level and PCa pathological parameters was also evaluated. Besides, ROR expression in PCa cells was further verified by qRT-PCR, and ROR knockdown model was constructed using lentivirus in PCa cell lines including PC-3 and Lncap. Cell counting kit-8 (CCK-8), transwell invasion and cell scratch assay were used to analyze the effect of ROR on the biological function of PCa cells and explore its underlying mechanism. QRT-PCR results demonstrated that ROR levels in PCa tissues were notably higher than that in normal ones, and the difference was statistically significant. Compared with patients with lowly-expressed ROR, patients with high ROR level had relatively more advanced tumor stage, higher incidence of lymph node or distant metastasis. Similarly, compared with negative control group, the cell proliferation, invasion and metastasis ability of the ROR knockdown group was significantly decreased. In addition, qRT-PCR results indicated that the expression of Akt, the key protein in the Akt signaling pathway, was significantly reduced in si-ROR cell lines. Furthermore, rescue experiment revealed that there was a mutual regulation between ROR and Akt. LncRNA ROR expression is strikingly increased in PCa tissues or cells, and is considerably associated with PCa stage, lymph node and distant metastasis. Additionally, LncRNA ROR may promote PCa cell proliferation, invasion and migration by regulating Akt.

Inhibiting lncRNA ROR suppresses growth, migration and angiogenesis in microvascular endothelial cells by up-regulating miR-26.

Lower extremity arteriosclerosis is one of leading causes of death worldwide. Arteriosclerosis is closely related to microvascular endothelial cells. This study was aimed to explore the role of long non-coding RNA ROR in regulations of growth, migration, and angiogenesis of microvascular endothelial cells. Angiogenesis was determined by the number of tube-like cells on a matrigel extracellular matrix. Cell viability, apoptosis, and migration were determined by CCK-8 assay, PI/FITC-Annexin V staining method, and transwell assay, respectively. Relative RNA expression of ROR, miR-26, and angiogenesis-associated genes were analyzed by qRT-PCR. The protein expression of apoptosis- and angiogenesis-associated genes, as well as main factors in NF-κB and JAK1/STAT3 pathways, were analyzed by Western blot. LncRNA ROR silence inhibited viability, migration, and angiogenesis of HMEC-1 cells but promoted apoptosis of them. miR-26 expression was promoted after knocking down ROR expression. miR-26 overexpression enhanced the inhibitory effects of ROR silence on growth, migration, and angiogenesis in HMEC-1 cells, whereas, miR-26 silence impaired the effects of ROR silence. Finally, we found that NF-κB and JAK1/STAT3 signaling pathways were inhibited by ROR down-regulation. Similarly, miR-26 overexpression enhanced the inhibitory effect of ROR down-regulation on the pathways and miR-26 inhibition abrogated it. Down-regulating lncRNA ROR inhibited growth, migration and angiogenesis of microvascular endothelial cells possibly through up-regulation of miR-26. During this process, the activations of NF-κB and JAK1/STAT3 pathways were inhibited after interaction of ROR and miR-26.

Long noncoding RNA ROR promotes breast cancer by regulating the TGF-\u03b2 pathway

BackgroundBreast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical regulators of fundamental cellular processes in a variety of tumors including breast cancer. The functional details of these regulatory elements, however, remain largely unexplored.MethodsIn this study, lncRNA ROR (linc-ROR) was examined by real-time PCR in different breast cancer cell lines and breast tumor tissues/non-tumor tissues were collected from both breast cancer patients and healthy controls. Linc-ROR was knockdown in breast cancer cell lines and the effects on cell proliferation, migration and invasion were tested both in vitro and in vivo tumor model. Effects of linc-ROR knockdown on TGF-β signaling pathway were investigated by Western blot.ResultsOur studies have suggested that linc-ROR, a critical factor for embryonic stem cell maintenance, probably acts as an oncogenic factor in breast cancer cells, causing poor prognostic outcomes. Overexpression of linc-ROR seems to be responsible for promoting proliferation and invasion of cancer cells as well as tumor growth in nude mice. The regulatory action of linc-ROR can affect the activity of the TGF-β signaling pathway, which has been proven critical for mammary development and breast cancer.ConclusionsThe results have highlighted the potential importance of linc-ROR in the progression of advanced breast cancer, and thus will stimulate efforts in the development of novel diagnostic and therapeutic strategies.

Long non-coding RNA ROR promotes radioresistance in hepatocelluar carcinoma cells by acting as a ceRNA for microRNA-145 to regulate RAD18 expression

Radiotherapy plays a limited role in the treatment of hepatocellular carcinoma (HCC) due to the development of resistance. Therefore, further investigation of underlying mechanisms involved in HCC radioresistance is warranted. Increasing evidence shows that long non-coding RNAs (linc-RNAs) are involved in the pathology of various tumors, including HCC. Previously, we have shown that long noncoding RNA regulator of reprogramming (linc-ROR) promotes HCC metastasis via induction of epithelial-mesenchymal transition (EMT). However, the roles of linc-ROR in HCC radioresistance and its possible mechanisms are unclear. Here, we established two radioresistant HCC cell lines (HepG2-R and SMMC-7721-R) and found that linc-ROR was significantly upregulated in radioresistant HCC cells. Knockdown of linc-ROR reduces in vitro and in vivo radiosensitivity of parental HCC cells by reducing DNA repair capacity, while ectopic expression of linc-ROR enhances radiosensitivity of radioresistant HCC cells. Further mechanistic investigations revealed that lincRNA-ROR exerted its biological effects by acting as a competing endogenous RNA (ceRNA) for miR-145 to regulate RAD18 expression, thereby promoting DNA repair. Collectively, our findings demonstrate that linc-ROR promotes HCC radioresistance and targeting it will be a promising strategy for enhancing the efficacy of radiotherapies in HCC.

Large Intergenic Non-coding RNA-RoR Inhibits Aerobic Glycolysis of Glioblastoma Cells via Akt Pathway.

Reprogramming energy metabolism is a hallmark of malignant tumors, including glioblastoma (GBM). Aerobic glycolysis is often utilized by tumor cells to maintain survival and proliferation. However, the underlying mechanisms of aerobic glycolysis in GBM remain elusive. Herein, we demonstrated that large intergenic non-coding RNA-RoR (LincRNA-RoR) functioned as a critical suppressor to inhibit the aerobic glycolysis and viability of GBM cells. We found that LincRNA-RoR was markedly reduced in GBM tissues compared with adjacent non-tumor tissues from 10 cases of GBM patients. Consistently, LincRNA-RoR expression in GBM cells was significantly lower than that in normal glial cells. The aerobic glycolysis of GBM cells, as determined by the measurement of glucose uptake and lactate production, was impaired by LincRNA-RoR overexpression. Mechanistically, LincRNA-RoR inhibited the expression of Rictor, the key component of mTORC2 (mammalian target of rapamycin complex 2), to suppress the activity of Akt pathway and impair the expression of glycolytic effectors, including Glut1, HK2, PKM2 and LDHA. Finally, enforced expression of LincRNA-RoR reduced the proliferation of GBM cells in vitro, restrained tumor growth in vivo, and repressed the expression of glycolytic molecules in GBM xenografts. Collectively, our results underscore LincRNA-RoR as a new suppressor of GBM aerobic glycolysis with therapeutic potential.