Identification and validation of potential prognostic lncRNA biomarkers for predicting survival in patients with multiple myeloma

Dong

et al. 2017

Oncology Letters

Abstract.It has previously been demonstrated that the long non-coding RNA (lncRNA) nuclear enriched abundant transcript (NEAT)-1 is increased in multiple cancers and may be associated with cancer development. However, the function and mechanism of NEAT1 in non-small cell lung cancer (NSCLC) has not yet been fully elucidated. In the present study, the expression of NEAT1 in NSCLC was detected using quantitative polymerase chain reaction and association with survival was estimated. The effect of NEAT1 on proliferation was detected by growth curve and cell cycle analysis. Bioinformatics analysis was used to identify miRNAs that interact with NEAT1. Following this, a series of molecular biological techniques were used to verify the mechanism of NEAT1. The results indicated that NEAT1 was highly expressed in NSCLC, and high NEAT1 expression was associated with a shorter overall survival. NEAT1 promoted NSCLC cell growth and affected the cell cycle process in vitro. Furthermore, NEAT1 was observed to bind hsa-miR-377-3p, functioning as a competing endogenous RNA, which resulted in de-repression of its target gene E2F transcription factor 3 (E2F3). E2F3, as an oncogene, may promote NSCLC progression. These results suggested that NEAT1 may promote the development of NSCLC through the miR-377-3p-E2F3 pathway.

Section: Methodsmentioning

confidence: 99%

“…Moreover, lncRNAs also have the potential function as diagnostic or prognostic markers of cancer (4)(5)(6)(7)(8)(9)(10). Nuclear enriched abundant transcript 1 (NEAT1) is a nuclear-restricted lncRNA that has two isoforms: NEAT1-1 and NEAT1-2 (11).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA NEAT1 regulates E2F3 expression by competitively binding to miR-377 in non-small cell lung cancer

Dong

et al. 2017

Oncology Letters

“…Gene expression profilings of highly purified bone marrow plasma cells performed in newly diagnosed patients with MM, GSE24080, 22 were downloaded from Gene Expression Omnibus (GEO) database (http://www.ncbi. nlm.nih.gov/geo/).…”

Section: Data Source and Patient Informationmentioning

confidence: 99%

Potential prognostic long non-coding RNA identification and their validation in predicting survival of patients with multiple myeloma

Huang

et al. 2017

Tumour Biol.

Multiple myeloma, a typical hematological malignancy, is characterized by malignant proliferation of plasma cells. This study was to identify differently expressed long non-coding RNAs to predict the survival of patients with multiple myeloma efficiently. Gene expressing profiles of diagnosed patients with multiple myeloma, GSE24080 (559 samples) and GSE57317 (55 samples), were downloaded from Gene Expression Omnibus database. After processing, survival-related long non-coding RNAs were identified by Cox regression analysis. The prognosis of multiple myeloma patients with differently expressed long non-coding RNAs was predicted by Kaplan-Meier analysis. Meanwhile, stratified analysis was performed based on the concentrations of serum beta 2-microglobulin (S-beta 2m), albumin, and lactate dehydrogenase of multiple myeloma patients. Gene set enrichment analysis was performed to further explore the functions of identified long non-coding RNAs. A total of 176 long non-coding RNAs significantly related to the survival of multiple myeloma patients (p < 0.05) were identified. In dataset GSE24080 and GSE57317, there were 558 and 55 patients being clustered into two groups with significant differences, respectively. Stratified analysis indicated that prediction of the prognoses with these long non-coding RNAs was independent from other clinical phenotype of multiple myeloma. Gene set enrichment analysis-identified pathways of cell cycle, focal adhesion, and G2-M checkpoint were associated with these long noncoding RNAs. A total of 176 long non-coding RNAs, especially RP1-286D6.1, AC008875.2, MTMR9L, AC069360.2, and AL512791.1, were potential biomarkers to evaluate the prognosis of multiple myeloma patients. These long non-coding RNAs participated indispensably in many pathways associated to the development of multiple myeloma; however, the molecular mechanisms need to be further studied.

“…It has been revealed that lncRNAs are involved in the development and progression of tumors, and that their abnormal expression is associated with tumor proliferation, apoptosis, the cell cycle, angiogenesis, recurrence and metastasis in numerous different types of cancer (4,5). Previous studies have demonstrated the potential roles of lncRNAs to serve as diagnostic markers and therapeutic targets for cancers (6)(7)(8)(9)(10)(11)(12)(13)(14). However, the role and mechanism of lncRNAs in ECC remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome analysis reveals dysregulated long non‑coding RNAs and mRNAs associated with extrahepatic cholangiocarcinoma progression

et al. 2017

Oncol Lett

Abstract. The incidence of extrahepatic cholangiocarcinoma (ECC) is the highest of all the cholangiocarcinoma cases. However, the molecular mechanism of ECC genesis and progression remains unclear. Long non-coding RNAs (lncRNAs) have been revealed to perform critical regulatory roles in cancer biology. In order to understand lncRNA expression patterns and their potential function in ECC, a transcriptome analysis of lncRNA and mRNA expression was performed in ECC and paired adjacent non-cancerous tissues using Agilent human lncRNA + mRNA arrayV4.0 (4x180 K format). It was identified that 268 lncRNAs and 459 mRNAs were differentially expressed in ECC. Among these, 78 lncRNAs and 66 mRNAs were upregulated >2-fold compared with adjacent non-cancerous tissues, and 190 lncRNAs and 393 mRNAs were downregulated in the ECC samples. Differences in lncRNA expression between ECC and paired adjacent non-cancerous tissues were confirmed using reverse transcription-quantitative polymerase chain reactionas proof of principle. Functional analysis of co-expressed mRNAs with lncRNAs indicated that these dysregulated lncRNAsmay be involved in known ECC-associated biological processes and pathways. The present findings indicated that mRNAs and lncRNAs perform important roles in the development and progression of ECC.The present findings may lay the foundation for future efforts to understand the role of lncRNAs and develop novel biomarkers in ECC IntroductionExtrahepatic cholangiocarcinoma (ECC) is a highly malignant cancer, representing ~80% of all cholangiocarcinoma clinical cases. In previous years, the incidence and mortality of ECC has continued to increase worldwide (1). Although continued advances in surgical techniques and treatment strategies have been achieved, the 5-year survival rate for patients who undergo surgical resection has been reported to be only 20-40% (2,3). The main reasons for the poor prognosis of ECC are a low rate of early diagnosis, fast progression and a high rate of recurrence. There is currently no effective method to improve the diagnosis and treatment of ECC, and the major cause of the molecular pathogenesis of oncogenesis and the progression of ECC remains largely unclear.Long non-coding RNAs (lncRNAs) are a large class of ncRNAs. It has been revealed that lncRNAs are involved in the development and progression of tumors, and that their abnormal expression is associated with tumor proliferation, apoptosis, the cell cycle, angiogenesis, recurrence and metastasis in numerous different types of cancer (4,5). Previous studies have demonstrated the potential roles of lncRNAs to serve as diagnostic markers and therapeutic targets for cancers (6)(7)(8)(9)(10)(11)(12)(13)(14). However, the role and mechanism of lncRNAs in ECC remains largely unknown. Via transcriptome analysis, the present study aimed to investigate lncRNA and mRNA expression that is up-or downregulated in ECC tissues compared with paired peritumoral tissues. Additional bioinformatics analysis and validation studies were performed to revea...