The Long Noncoding RNA PANDAR as a Prognostic and Diagnostic Biomarker in Panceratic Cancer .

Pancreatic cancer (PC) is a lethal complication in the world, affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Most PC patients are confronted with locally metastatic or advanced diseases in the asymptomatic phase, and about 80% have late diagnosis with metastasis. Recently, long noncoding RNAs (lncRNAs) have drawn attention as a novel biological regulation layer. They take part in the regulation of mRNA and can be used as a prognostic factor or drug target. Based on their functions as regulators of PC initiation and progress, the lncRNAs can be categorized as tumor suppressors or oncogenic. They can be considered as a target for finding new biomarkers for prognosis, diagnosis, monitoring, and treating drug response in PC. Therefore, the present study summarizes the lncRNAs role in PC and the probable strategies to deal with their expression and controlling tumorigenesis and detection of the prognosis of PC.

Cisplatin-induced PANDAR-Chemo-EVs contribute to a more aggressive and chemoresistant ovarian cancer phenotype through the SRSF9-SIRT4/SIRT6 axis.

OBJECTIVE: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. METHODS: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatin-resistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich pre-mRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. RESULTS: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. CONCLUSION: Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

LncRNA-PANDAR regulates the progression of thyroid carcinoma by targeting miR-637/KLK4.

Thyroid gland carcinoma (TC) originates from follicular or parafollicular thyroid cells and is one of the most common endocrine organ malignancies. To explore the molecular mechanism by which long-chain non-coding RNAs regulate the growth and metastasis of thyroid gland carcinoma, in this study we focused on long non-coding RNAs (lncRNAs) that have been reported to be involved in tumorigenesis. We identified Promoter Region of CDKN 1A antisense DNA damage-activated RNA (PANDAR), which was positively correlated with thyroid gland carcinoma risk. PANDAR could promote thyroid gland carcinoma cell proliferation and metastasis. PANDAR negatively correlated with miR-637, and miR-637 overexpression suppressed thyroid gland carcinoma progression, which could be reversed by PANDAR. MiR-637 could target Kallikrein-related peptidases 4 (KLK4) to inhibit its expression, which was high in thyroid gland carcinoma. KLK4 inhibited cell progression in thyroid gland carcinoma cells. Knockdown of PANDAR expression inhibited cancer progression in nude mice. Overall, PANDAR can suppress miR-637 and induce KLK4 to regulate invasion and migration in thyroid gland carcinoma. Additionally, we identified miR-637 as a target of PANDAR in thyroid gland carcinoma, and PANDAR can be used as a novel therapeutic target for the treatment of thyroid gland carcinoma.

Knockdown of LncRNA PANDAR by CRISPR-dCas9 Decreases Proliferation and Increases Apoptosis in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial tumor in the oral cavity. Emerging evidence has demonstrated the important function roles of long noncoding RNAs (lncRNAs) in human cancers. LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) functions as an oncogene in multiple carcinomas, whereas its function in OSCC has not been investigated yet. The aim of our study is to investigate the possible regulatory mechanism of PANDAR in OSCC. First of all, PANDAR was highly expressed in OSCC cells and loss-of-function assays mediated by CRISPR-dCas9 observed that PANDAR silencing restrained cell proliferation and promoted cell apoptosis. Then we found and confirmed the interaction between PANDAR and serine and arginine rich splicing factor 7 (SRSF7). Subsequently, serine/threonine-protein kinase pim-1 (PIM1) was proved to be regulated by PANDAR in SRSF7-dependant way. Rescue experiments validated that PANDAR modulated the proliferation and apoptosis in OSCC through PIM1. In conclusion, PANDAR bound with SRSF7 to increase PIM1 expression, hence promoting the development of OSCC. These data shed new lights into the seeking for effective diagnostic biomarkers and therapeutic targets for OSCC patients.

Regulatory roles of lncRNA PANDAR in breast cancer cell proliferation.

Background: Breast cancer represents the second most deadly malignancy in women, and long noncoding RNAs (lncRNAs) have crucial functions in its development. Objective: To investigate effects of the promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) on epithelial-mesenchymal transition (EMT) in breast cancer cells and their proliferation. Methods: lncRNAs potentially regulating the transcriptional activity of the E-cadherin (E-cad, an epithelial cell marker) gene promoter were screened using a dual-luciferase reporter assay. PANDAR was overexpressed in Michigan cancer foundation 7 (MCF-7) breast cancer cells. E-cad and N-cadherin (N-cad, a mesenchymal cell marker) levels were detected by immunoblotting. Cell viability was assessed using a cell counting kit-8. Results: PANDAR and TCONS00068220/LOC105375819 conservatively regulated the promoter activity of E-cad. PANDAR overexpression in MCF-7 inhibited E-cad expression, but upregulated N-cad. The enhanced expression of PANDAR promoted cell proliferation. Conclusion: PANDAR is a key transcriptional repressor of E-cad and has regulatory effects on the promotion of cell proliferation. PANDAR is an oncogene in breast cancer, potentially facilitating the EMT process and promoting cell proliferation.

Long noncoding RNA PANDAR inhibits the development of lung cancer by regulating autophagy and apoptosis pathways.

Background: LncRNAs has been shown to play important roles in the progression of lung cancer, but it remains poorly understood whether lncRNAs affect the occurrence and development of lung cancer by regulating autophagy and apoptosis levels. Here, we investigated the roles of PANDAR in NSCLC. Materials and Methods: The expression profile and clinical application of PANDAR and its possible target gene BECN1 were tested in 276 cases of lung cancer tissues. Through some actual experiments, we explored functions of PANDAR about proliferation, apoptosis and autophagy of NSCLC cells in vitro. Results: PANDAR was found to downregulate both in lung cancer tissues and cell lines compared with corresponding controls (P < 0.05 for all), which was related to tumor stage (P < 0.05). Moreover, autophagy related gene BECN1 was also downregulated in lung cancer tissues comparison with normal tissues (P < 0.01), and there was a significant positive correlation between PANDAR and BECN1 levels (r = 0.789, P < 0.001). So, the high expression of PANDAR increased BECN1 expression levels and impaired the proliferation of NSCLC cell lines in vitro. Furthermore study showed PANDAR could regulate cell autophagy and apoptosis levels. Conclusion: These results indicated lncRNA PANDAR was a tumor suppressor and can inhibit NSCLC cell proliferation by activating autophagy and apoptosis pathways via upregulation of BECN1 expression.

Expression Levels of lncRNAs in the Patients with the Renal Transplant Rejection.

PURPOSE: Long non-coding RNAs (lncRNAs) include a vast portion of human transcripts. They exert regulatory roles in immune responses and participate in diverse biological functions. Recent studies indicated dysregulation of lncRNAs in the process of transplant rejection. In the current study, we aimed at identification of the expression of five lncRNAs (OIP5-AS1, FAS-AS1, TUG1, NEAT1 and PANDAR) in association with the process of transplant rejection. MATERIAL AND METHODS: We assessed expression of these lncRNAs in the peripheral blood of 61 kidney transplant receivers including 29 transplant rejected patients and 32 transplant non-rejected patients using real time PCR technique. RESULTS: Expression of FAS-AS1 was significantly higher in rejected group compared to non-rejected group in males, however, differences between case and control groups were insignificant among females. For other lncRNAs no significant differences were detected between two study groups. Quantile regression model showed that patients' gender was an important parameter in determination of FAS-AS1 expression (Beta=-9.46, t=-2.82, P=0.007) but not for other lncRNAs expressions. Significant pairwise correlations were detected between expression levels of lncRNAs in a disease related manner. CONCLUSION: Based on the higher expression of FAS-AS1 in patients with transplant rejection, this lncRNA might be associated with the pathogenesis of renal transplant rejection.

Prognostic and Clinicopathological Significance of Long Non-coding RNA PANDAR Expression in Cancer Patients: A Meta-Analysis.

Background: Long non-coding RNA PANDAR is an emerging non-coding RNA mapping to 6p21.2. It underlies metastatic progression and chromosomal instability in a variety of cancers. Despite the fact that recent studies have revealed that lncRNA PANDAR may be a potential prognostic biomarker for patients with cancer, there has still been controversy on the prognostic value of PANDAR. Methods: Databases of PubMed, Embase, SinoMed, and Web of Science were carefully searched and the literature which investigated the prognostic value of PANDAR expression among human cancers was collected for further analysis. Odds ratios (ORs) or hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled to estimate the relation between PANDAR expression and survival or clinicopathological characteristics of cancer patients. Results: There were 13 eligible studies in total, with 1,465 patients enlisted in this meta-analysis. All the eligible studies complied with the case-control study. The outcome showed that the elevated expression level of PANDAR was significantly related to poor overall survival (OS) (pooled HR 1.72, 95%CI 1.14-2.60). However, high or low expression of PANDAR did not differ in the prediction of event-free survival (EFS). Moreover, we discovered that high PANDAR expression was closely related to decreased OS in colorectal cancer (pooled HR 3.43, 95%CI 2.06-5.72) and reduced expression level of PANDAR was markedly related to poor OS (pooled HR 0.65, 95%CI 0.45-0.88) in non-small cell lung cancer. However, the expression level of PANDAR had no significant association with OS in renal cell carcinoma (pooled HR 1.19, 95%CI 0.56-2.50). Moreover, after analysis, we discovered that the high expression level of PANDAR was associated closely with the depth of invasion (pooled OR 3.95, 95%CI 2.36-6.63), lymph node metastasis (pooled OR 1.92, 95%CI 0.93-3.98), tumor stage (pooled OR 2.05, 95%CI 0.99-4.27), and distant metastasis (pooled OR 2.87, 95%CI 1.60-5.16). Conclusions: Our study revealed that increased PANDAR expression may serve as an adverse prognostic biomarker for cancer patients, thus helping the clinical decision-making process.

Plasma long noncoding RNAs PANDAR, FOXD2-AS1, and SMARCC2 as potential novel diagnostic biomarkers for gastric cancer.

BACKGROUND: Gastric cancer is still a common cancer worldwide. Investigation of potential plasma biomarkers for gastric cancer diagnosis is essential for prevention strategies and early intervention for gastric cancer-control planning. OBJECTIVES: This study was aimed to explore the lncRNAs' promoter of CDKN1A antisense DNA-damage-activated RNA (PANDAR), FOXD2-AS1, and SMARCC2 as potential novel diagnostic biomarkers for gastric cancer. METHOD: 109 gastric cancer patients and 106 healthy controls were involved in this study. Plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 were detected by real-time PCR. Student's t-test, Mann-Whitney U test, and Chi-square test were used to verify the differences of clinical variables between two groups. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of every biomarker. Multivariable analysis of risk factors for gastric cancer was performed using logistic regression analysis. RESULTS: There were significant differences in age, gender, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 153 between gastric cancer and healthy controls (P<0.05). Compared with healthy subjects, the levels of plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 were all significantly higher in gastric cancer patients (P<0.05). These lncRNAs were significantly associated with clinicopathological parameters of gastric cancer, like pathological differentiation, TNM stage, and/or lymph nodes metastasis, and/or invasion depth (P<0.05). The AUC for lncRNA PANDAR was 0.767, for FOXD2-AS1 was 0.700, for SMARCC2 was 0.748, and the AUC of the combinative diagnostic value of these three lncRNAs was 0.839. Adjusted by other variables, these lncRNAs' expressions were significantly associated with gastric cancer. CONCLUSIONS: Plasma lncRNAs PANDAR, FOXD2-AS1, and SMARCC2 might be appropriate diagnostic biomarkers for gastric cancer.

Inhibition of lncRNA PANDAR reduces cell proliferation, cell invasion and suppresses EMT pathway in breast cancer.

BACKGROUND: The PANDAR, a novel identified long non-coding RNA, is previously reported to function as oncogene in various cancers including breast cancer. the study aims to explore the role of lncRNA PANDAR for cell proliferation and invasion of breast cancer, and its underlying mechanism. METHODS: The expression of lncRNA PANDAR in 65 pairs of breast cancer tissues and adjacent normal tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) assay. The association between lncRNA PANDAR expression and clinical factors of breast cancer was analyzed. Cell proliferation, cell colony formation and cell invasion assays were performed to detect the effects of lncRNA PANDAR expression tumor proliferation and invasion abilities. The western blot analysis was also performed to detected the EMT related makers expression of E-cadherin, Vimentin, MMP2 and MMP9. RESULTS: We demonstrated that lncRNA PANDAR expression was higher in breast cancer tissues and cells compared with adjacent normal tissues and the normal mammary epithelial cell line, respectively. Higher lncRNA PANDAR expression positively associated with lymph node metastasis and advanced clinical stage in patients. In vitro, we demonstrated that knockdown of lncRNA PANDAR significantly suppressed cell proliferation, cell colony formation and cell invasion ability in breast cells. Furthermore, we verified that knockdown of lncRNA PANDAR dramatically inhibited cell epithelial-mesenchymal transition (EMT) pathway by downregulating Vimentin, MMP2 and MMP9 expression, but upregulating E-cadherin expression in breast cancer. CONCLUSIONS: Our results proved that PANDAR may serve as potential target of breast cancer treatment.

The prognostic and therapeutic values of long noncoding RNA PANDAR in colorectal cancer.

Long noncoding RNAs (lncRNAs) consist of 200 nucleotide sequences that play essential roles in different processes, including cell proliferation, and differentiation. There is evidence showing that the dysregulation of lncRNAs promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) leads to the development and progression in several cancers including colorectal cancer, via p53-dependent manner. This suggests that these lncRNAs may be of value as prognostic indices and a therapeutic target, as a high expression of lncRNAs PANDAR is associated with poor prognosis. Furthermore, modulating lncRNAs PANDAR has been reported to induce apoptosis and inhibit the tumor growth through modulation of cell cycle and epithelial-mesenchymal transition (EMT) pathway. The aim of the current review was to provide an overview of the prognostic and therapeutic values of lncRNAs PANDAR in colorectal cancer.

Clinicopathological and prognostic value of lncRNA PANDAR expression in solid tumors: Evidence from a systematic review and meta-analysis.

PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) has been shown to be aberrantly expressed in many types of cancer. Considering conflicting data, the current study was aimed to assess its potential role as a prognostic marker in malignant tumors. A comprehensive literature search of PubMed, Medline, and Web of Science was performed to identify all eligible studies describing the use of PANDAR as a prognostic factor for different types of cancer. Data related to overall survival (OS) and clinicopathologic features were collected and analyzed. The pooled hazard ratio (HR) and odds radio (OR) with a 95% confidence interval (CI) were used to estimate associations. Ten original studies containing 1,231 patients were included. The results showed that in patients with cancer, high PANDAR expression is correlated with lymph node metastasis (LNM; OR = 2.57; 95% CI, 1.76-3.81; p < 0.001), tumor stage (OR = 2.90; 95% CI, 1.25-6.75; p = 0.013), and tumor size (OR = 1.79; 95% CI, 1.11-2.91; p = 0.018). However, sensitivity analysis further demonstrated a significant association between high PANDAR expression and OS, both in multivariate and univariate analysis models (pooled HR 2.01; 95% CI, 1.17-3.44 and pooled HR 2.62; 95% CI, 1.98-3.47, respectively), after omitting one study. These results suggested that PANDAR expression might be indicative of advanced disease and poor prognosis in patients with cancer. Further studies are necessary to determine the value of this risk stratification biomarker in clinical management of patients with cancer.

Effects of hyperthermia on PANDAR, LncRNA-p21 and ST8SIA gene in A549 Cell / 中国职业医学

OBJECTIVE: To investigate the effect of hyperthermia on the expression of PANDAR, LncRNA-p21 and ST8SIA genes in the human lung adenocarcinoma A549 cells. METHODS: A549 cells were randomly divided into 4 groups. The A549 cells in control group were cultured at 37 ℃; the cells at experimental groups were cultured at 40, 42 or 44 ℃ respectively. The cells in these 4 groups were incubated for 1 hour, and the levels of PANDAR, LncRNA-p21 and ST8SIA genes were analyzed by real-time fluorescence quantitative polymerase chain reaction. RESULTS: In cells cultured at 40, 42 or 44 ℃ experimental groups, the relative expression of PANDAR gene was lower than that of control group(P<0.05). In cells cultured at 44 ℃ experimental group, the relative expression of PANDAR gene was lower than that of the 40 and 42 ℃ experimental groups(P<0.05). There was no significant change in the relative expression of LncRNA-p21 and ST8SIA genes among the four groups(P>0.05). CONCLUSION: Hyperthermia decrease the expression of PANDAR gene in A549 cells.

Overexpression of lncRNA PANDAR predicts adverse prognosis in acute myeloid leukemia.

BACKGROUND AND PURPOSE: Abundant studies have shown that lncRNA PANDAR plays an oncogenic role in human solid tumors. Although abnormal expression of PANDAR has been well investigated in solid tumors, it was rarely studied in hematologic diseases. Hence, the aim of this study was to determine the PANDAR expression level and its clinical significance in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: For detecting the expression level of PANDAR in 119 AML patients and 26 controls, real-time quantitative PCR was used in this study. The prognostic values were evaluated by using Kaplan-Meier analysis, Cox regression analyses, and logistic regression analysis. RESULTS: PANDAR was significantly overexpressed in AML and might be a promising biomarker which could distinguish AML from normal samples (P<0.001). Patients with high expression of PANDAR (PANDAR high) were older and showed higher bone marrow blasts than patients in PANDAR low group (P=0.029 and 0.032, respectively). Significant differences between these groups were also detected regarding risk group and karyotype finding (P=0.009 and 0.041, respectively). Importantly, PANDAR high patients presented a significant lower complete remission rate compared to PANDAR low patients (P<0.001). Furthermore, Kaplan-Meier analysis showed that PANDAR high patients had shorter overall survival compared to PANDAR low patients observing the whole AML cohort, and also in the non-M3 group of patients (P<0.001 and P=0.005, respectively). Multivariate analysis of Cox and logistic regression analysis confirmed that high PANDAR expression was an independent unfavorable risk factor for overall survival and complete remission in both observed patient groups. CONCLUSION: These results revealed that PANDAR was overexpressed in AML, and that higher PANDAR expression was associated with poor clinical outcome. Our study therefore suggests that PANDAR expression is a promising biomarker for prognostic prediction for AML.

SP1-induced upregulation of lncRNA PANDAR predicts adverse phenotypes in retinoblastoma and regulates cell growth and apoptosis in vitro and in vivo.

Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription. Furthermore, in vitro and in vivo studies were induced to elucidate the biological functions of PANDAR. The results indicated that PANDAR was increased in RB tissues and cells, and this upregulation was associated with advanced IIRC stage, positive optic nerve invasion, and lower differentiation grade in RB patients. In addition, SP1 could bind directly to the PANDAR promoter region and activate its transcription. Furthermore, PANDAR silencing yielded tumor suppressive effects both in vitro and in vivo. Importantly, PANDAR protects against apoptosis partly by affecting Bcl-2/caspase-3 pathway. Ultimately, our work first illustrate that PANDAR plays an oncogenic role in RB and may offer a potential therapeutic target for treating this devastating disease.

Long non-coding PANDAR as a novel biomarker in human cancer: A systematic review.

OBJECTIVES: Long non-coding RNAs (lncRNAs) are characterized as a group of RNAs that more than 200 nucleotides in length and have no protein-coding function. More and more evidences provided that lncRNAs serve as key molecules in the development of cancer. Deregulation of lncRNAs functions as either oncogenes or tumour suppressor genes in various diseases. Recently, increasing studies about PANDAR in cancer progression were reported. In our review, we will focus on the current research on the character of PANDAR include the clinical management, tumour progression and molecular mechanisms in human cancers. MATERIALS AND METHODS: We summarize and analyze current studies concerning the biological functions and mechanisms of lncRNA PANDA in tumour development. The related studies were obtained through a systematic search of Pubmed. RESULTS: PANDAR was a well-characterized oncogenic lncRNA and widely overexpressed in many tumours. PANDAR is upregulated in many types of cancer, including colorectal cancer, lung cancer, renal cell carcinoma, cholangiocarcinoma, osteosarcoma, thyroid cancer and other cancers. Upregulation of PANDAR was significantly associated with advanced tumour weights, TNM stage and overall survival. Furthermore, repressed of PANDAR would restrain proliferation, migration and invasion. CONCLUSION: PANDAR may act as a powerful tumour biomarker for cancer diagnosis and treatment.

Long non-coding RNA PANDAR promotes melanoma cell invasion through regulating epithelial-mesenchymal transition.

Melanoma is a malignant skin tumor and has a poor cure rate because of its high metastatic potential. Overexpression of long non-coding (lnc) RNA PANDAR has been observed in several kinds of cancer, but the function of PANDAR on melanoma is still unclear. Therefore, this study was to explore the mechanism of PANDAR on the occurrence and progression in malignant melanoma. We detected expression of PANDAR in malignant melanoma tissues and cell lines by qRT-PCR and analyzed correlation of PANDAR expression with the patients' prognosis. Furthermore, we investigated the effects of PANDAR on cell viability, migration, invasion, tumorigenesis, and epithelial-mesenchymal transition (EMT) using CCK-8, Transwell, and nude mouse subcutaneous tumor formation model assays and Western blotting analysis, respectively. From the results, we discovered that the PANDAR expression is strikingly upregulated in melanoma tissues compared with paired-adjacent non-tumorous tissues and elevated PANDAR is positively correlated with short overall survival time. The results also demonstrate that knockdown of PANDAR inhibits cell viability, migration, invasion, tumorigenesis, and EMT, whereas overexpression of PANDAR gave opposite results by promoting cell viability, migration, invasion, tumorigenesis, and EMT of melanoma cells. These new findings all illustrate that PANDAR might play a pivotal oncogenic role in the occurrence and development of melanoma, and PANDAR might promote melanoma cell invasion through regulating EMT, providing a potential diagnostic and therapeutic target for melanoma.

Long non-coding RNA PANDAR overexpression serves as a poor prognostic biomarker in oral squamous cell carcinoma.

BACKGROUND: Long non-coding RNA (lncRNA) has been found to play a crucial role in carcinogenesis and in evaluating prognosis of multiple neoplasms. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA), a newly discovered cancer-associated RNA is abnormally expressed in a wide variety of tumors. Expression and the functional role of PANDAR in human oral squamous cell carcinoma (OSCC), however, needs to be completely elucidated. METHODS: Quantitative real-time PCR (qRT-PCR) was applied to detect expression levels of lncRNA PANDAR in OSCC tissues and corresponding paracancerous normal tissues in 92 OSCC patients, four OSCC cell lines, and a normal oral keratinocytes cell line. Association between expression of PANDAR and clinicopathological features of OSCC patients was also analyzed. For analysis of overall survival data, Kaplan-Meier curves were constructed. The prognostic value of PANDAR was examined by Cox regression analysis. PANDAR levels were knocked down in OSCC cell line Tca8113 by using PANDAR siRNA. Function of PANDAR on tumor cell proliferation, migration, and invasion was further evaluated by MTT and Transwell assays in vitro. RESULTS: PANDAR was highly expressed in OSCC tissues and cell lines (P < 0.05) and its high expression level was found to be closely associated with advanced TNM stage (P = 0.004) and positive distant metastasis (P = 0.001). Furthermore, overall survival rate of OSCC patients with high PANDAR expression was poorer than patients with low PANDAR expression (P < 0.001). Cox proportional hazards model analysis showed that expression level of PANDAR can be used as an independent prognostic indicator for OSCC. Functionally, knockdown of PANDAR can inhibit proliferation, invasion, and migration of OSCC cells. CONCLUSIONS: Our findings indicate that PANDAR may serve as a promising prognostic biomarker and a new molecular target for new therapies for OSCC patients.

The role of long non-coding RNA PANDAR in the occurrence and development of malignant tumors / 中国肿瘤生物治疗杂志

@# 长链非编码RNA（long non-coding RNA，lncRNA）最初被认为是不具有功能的“转录噪声”，但越来越多的研究发现， lncRNA的失调在很多肿瘤中起着癌基因或抑癌基因的作用，是癌症发展的关键分子。PANDAR作为一种重要的lncRNA受到了 诸多关注。有研究证明，PANDAR在许多肿瘤中特异性表达，在大多数肿瘤中上调，但在非小细胞肺癌中显著下调，PANDAR的 特异性表达与肿瘤大小、TNM分期和总生存率显著相关。本文通过对lncRNAPANDAR在恶性肿瘤细胞中的主要作用模式、 表 达情况、作用机制及对各类肿瘤发生发展的影响进行综述，旨在为临床恶性肿瘤生物学诊治疗提供新的靶标。

LncRNA PANDAR as a prognostic marker in Chinese cancer.

BACKGROUND: LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the efficacy of PANDAR as a prognostic marker in malignant tumors. METHODS: The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between PANDAR expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between PANDAR expression and pathological parameters. RESULTS: Eight original studies covering 1,132 cancer patients were included. The pooled HR suggested that high PANDAR expression correlated with poor OS (pooled HR=1.60, 95% CI: 1.09-2.33) in cancer patients. PANDAR expression was also related to lymph node metastasis (OR=3.26, 95% CI: 2.09-5.09), advanced tumor stage (OR=3.60, 95% CI: 2.39-5.44) and histological grade (OR=2.75, 95% CI: 1.73-4.38). Begg's funnel plot showed no evidence of obvious asymmetry for overall survival and lymph node metastasis. CONCLUSIONS: Thus high PANDAR expression appears predictive of poor OS, lymph node metastasis, advanced tumor stage and histological grade in multiple cancers. This suggests PANDAR expression could serve as a biomarker of poor prognosis in Chinese cancer patients.