scholarly journals Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7120
Author(s):  
Anna Panza ◽  
Stefano Castellana ◽  
Giuseppe Biscaglia ◽  
Ada Piepoli ◽  
Luca Parca ◽  
...  

Fusion genes and epigenetic regulators (i.e., miRNAs and long non-coding RNAs) constitute essential pieces of the puzzle of the tumor genomic landscape, in particular in mechanisms behind the adenoma-to-carcinoma progression of colorectal cancer (CRC). In this work, we aimed to identify molecular signatures of the different steps of sporadic CRC development in eleven patients, of which synchronous samples of adenomas, tumors, and normal tissues were analyzed by RNA-Seq. At a functional level, tumors and adenomas were all characterized by increased activity of the cell cycle, cell development, cell growth, and biological proliferation functions. In contrast, organic survival and apoptosis-related functions were inhibited both in tumors and adenomas at different levels. At a molecular level, we found that three individuals shared a tumor-specific fusion named MRPS31-SUGT1, generated through an intra-chromosomal translocation on chromosome 13, whose sequence resulted in being 100% identical to the long non-coding RNA (lncRNA) MRPS31P5. Our analyses suggest that MRPS31P5 could take part to a competitive endogenous (ce)RNA network by acting as a miRNA sponge or/and as an interactor of other mRNAs, and thus it may be an important gene expression regulatory factor and could be used as a potential biomarker for the detection of early CRC events.

2020 ◽  
Vol 35 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Mingzhu Lin ◽  
Yinyan Li ◽  
Jianfeng Xian ◽  
Jinbin Chen ◽  
Yingyi Feng ◽  
...  

Objective: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1, has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer. Methods: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer. Results: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = −0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER, through acting as a competing endogenous RNA for miR-182 in colorectal cancer. Conclusion: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER, which may serve as a target for colorectal cancer diagnosis and treatment.


Neoplasma ◽  
2016 ◽  
Vol 63 (06) ◽  
pp. 984-990 ◽  
Author(s):  
J. LIU ◽  
J. WANG ◽  
Y. SONG ◽  
Y. YANG ◽  
Y. HU ◽  
...  

2020 ◽  
Author(s):  
Liangbao Xie ◽  
Guangfei Cui ◽  
Tao Li

Abstract Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.


2020 ◽  
Author(s):  
Yu-Hui Zhang ◽  
Wei-Bin Huang ◽  
Yu-Jie Yuan ◽  
Jin Li ◽  
Jing Wu ◽  
...  

Abstract Background Long non-coding RNA H19 was demonstrated to be significantly correlated with tumor metastasis. However, the specific functions of H19 in colorectal cancer (CRC) metastasis and the underlying mechanism are still largely unclear. Methods Use public database to screen the potential lncRNA crucial for metastasis in colorectal cancer. The expression of H19 in clinical CRC specimens was detected by qRT-PCR. The effect of H19 on the metastasis of CRC cells was investigated by transwell, wound healing assays, CCK-8 assays and animal studies. The potential proteins binding to H19 was identified by LC-MS and verified by RNA immunoprecipitation (RIP). The expression of indicated RNA and proteins were measured by qRT-PCR or western blot. Results We found the expression of lncRNA H19 was significantly upregulated in primary tumor and metastatic tissues, correlated with poor prognosis in CRC. Ectopic H19 expression promoted the metastasis of colorectal cancer cells in vitro and in vivo , and induced epithelial-to-mesenchymal transition (EMT). Mechanistically, H19 directly bound to hnRNPA2B1. Knockdown of hnRNPA2B1 attenuated the H19-induce migration and invasion in CRC cells. Furthermore, H19 stabilized and upregulated the expression of Raf-1 by facilitated the interaction between hnRNPA2B1 and Raf-1 mRNA, resulting in activation of Raf-ERK signaling. Conclusions Our findings demonstrate the role of H19/hnRNPA2B1/EMT axis in regulation CRC metastasis, suggested H19 could be a potential biomarker to predict prognosis as well as a therapeutic strategy for CRC.


2018 ◽  
Vol 33 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Heng Fan ◽  
Jian-hua Zhu ◽  
Xue-qing Yao

Background: Long non-coding RNA (lncRNA) plays a very important role in the occurrence and development of various tumors, and is a potential biomarker for cancer diagnosis and prognosis. The purpose of this study was to investigate the relationship between the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and the prognostic significance in patients with colorectal cancer. Methods: The expression of PVT1 was measured by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in cancerous and adjacent tissues of 210 colorectal cancer patients. The disease-free survival and overall survival of colorectal cancer patients were evaluated by Kaplan–Meier analysis, and univariate and multivariate analysis were performed by Cox proportional-hazards model. Results: Our results revealed that PVT1 expression in cancer tissues of colorectal cancer was significantly higher than that of adjacent tissues ( P<0.001). High PVT1 expression was increased by 51.4% (108/210), which was significantly correlated with the tumor differentiation, the depth of invasion, the stage of tumor, node, metastasis (TNM), and lymphatic metastasis. The Kaplan–Meier analysis showed that high PVT1 expression resulted in a shorter disease-free survival (Log-rank test P<0.001) and overall survival (Log-rank test P<0.001) compared with the low PVT1 expression group in colorectal cancer patients, whether at TNM I/II stage or at TNM III/IV stage. A multivariate Cox regression analysis demonstrated that high PVT1 expression was an independent predictor of poor prognosis in colorectal cancer patients. Conclusions: Our results suggest that high PVT1 expression might be a potential biomarker for assessing tumor recurrence and prognosis in colorectal cancer patients.


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