Silencing long non‑coding RNA, differentiation antagonizing non‑protein coding RNA promotes apoptosis and inhibits tumor growth in colon cancer

AbstractGemcitabine is the first-line chemotherapy drug for cholangiocarcinoma (CCA), but acquired resistance has been frequently observed in CCA patients. To search for potential long noncoding RNAs (lncRNAs) involved in gemcitabine resistance, two gemcitabine resistant CCA cell lines were established and dysregulated lncRNAs were identified by lncRNA microarray. Long intergenic non-protein coding RNA 665 (LINC00665) were found to rank the top 10 upregulated lncRNAs in our study, and high LINC00665 expression was closely associated with poor prognosis and chemoresistance of CCA patients. Silencing LINC00665 in gemcitabine resistant CCA cells impaired gemcitabine tolerance, while enforced LINC00665 expression increased gemcitabine resistance of sensitive CCA cells. The gemcitabine resistant CCA cells showed increased EMT and stemness properties, and silencing LINC00665 suppressed sphere formation, migration, invasion and expression of EMT and stemness markers. In addition, Wnt/β-Catenin signaling was activated in gemcitabine resistant CCA cells, but LINC00665 knockdown suppressed Wnt/β-Catenin activation. B-cell CLL/lymphoma 9-like (BCL9L), the nucleus transcriptional regulators of Wnt/β-Catenin signaling, plays a key role in the nucleus translocation of β-Catenin and promotes β-Catenin-dependent transcription. In our study, we found that LINC00665 regulated BCL9L expression by acting as a molecular sponge for miR-424-5p. Moreover, silencing BCL9L or miR-424-5p overexpression suppressed gemcitabine resistance, EMT, stemness and Wnt/β-Catenin activation in resistant CCA cells. In conclusion, our results disclosed the important role of LINC00665 in gemcitabine resistance of CCA cells, and provided a new biomarker or therapeutic target for CCA treament.

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Screening and survival analysis of melanoma immunodrug response-related genes and the function of magnetic nanoparticles in gene extraction

Materials Express ◽

10.1166/mex.2021.2037 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1306-1312

Author(s):

Li Song ◽

Ningchao Du ◽

Haitao Luo ◽

Furong Li

Keyword(s):

Survival Analysis ◽

Magnetic Nanoparticles ◽

Drug Response ◽

High Throughput Sequencing ◽

Cox Proportional Hazards ◽

Sequencing Data ◽

Protein Coding ◽

Non Coding Rna ◽

Long Non Coding Rna ◽

Rna Genes

This study aimed to identify the association of protein coding and long non coding RNA genes with immunotherapy response in melanoma. Based on RNA sequencing data of melanoma specimens, the expression levels of protein coding and long non coding RNA genes were calculated using the Kallisto RNA-seq quantification method, and differently expressed genes were detected using the DESeq2 method. Cox proportional hazards regression was used to evaluate the effects of gene expression on survival. According to the clinical data of 14 patients with drug response and 11 patients without drug response, 18 protein coding genes and 14 long non coding RNAs showed differential expressions (multiple of difference > 2 and P < 0.01 after correction), among which the coding genes of differential expression were significantly enriched through the process of cell adhesion (P < 0.01). The results of survival analysis showed that 18 coding genes and 14 long non coding RNA genes had significant effects on patient survival (P < 0.01). In this study, magnetic nanoparticles can be used to extract genomic DNA and total RNA due to their paramagnetism and biocompatibility, then transcriptome high-throughput sequencing was performed. The method has the advantages of removing dangerous reagents such as phenol and chloroform, replacing inorganic coating such as silica with organic oil, and shortening reaction time. Protein coding and long non coding RNA genes as well as magnetic nanoparticles may serve as potential cancer immune biomarker targets for developing future oncological treatments.

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Long non-coding RNA PTPRG-AS1 promotes cell tumorigenicity in epithelial ovarian cancer by decoying microRNA-545-3p and consequently enhancing HDAC4 expression

10.21203/rs.3.rs-51729/v3 ◽

2020 ◽

Author(s):

Juanjuan Shi ◽

Xijian Xu ◽

Dan Zhang ◽

Jiuyan Zhang ◽

Hui Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Epithelial Ovarian Cancer ◽

Cell Lines ◽

Luciferase Reporter ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Background: Long non-coding RNA PTPRG antisense RNA 1 (PTPRG-AS1) deregulation has been reported in various human malignancies and identified as an important modulator of cancer development. Few reports have focused on the detailed role of PTPRG-AS1 in epithelial ovarian cancer (EOC) and its underlying mechanism. This study aimed to determine the physiological function of PTPRG-AS1 in EOC. A series of experiments were also performed to identify the mechanisms through which PTPRG-AS1 exerts its function in EOC.Methods: Reverse transcription-quantitative polymerase chain reaction was used to determine PTPRG-AS1 expression in EOC tissues and cell lines. PTPRG-AS1 was silenced in EOC cells and studied with respect to cell proliferation, apoptosis, migration, and invasion in vitro and tumor growth in vivo. The putative miRNAs that target PTPRG-AS1 were predicted using bioinformatics analysis and further confirmed in luciferase reporter and RNA immunoprecipitation assays.Results: Our data verified the upregulation of PTPRG-AS1 in EOC tissues and cell lines. High PTPRG-AS1 expression was associated with shorter overall survival in patients with EOC. Functionally, EOC cell proliferation, migration, invasion in vitro, and tumor growth in vivo were suppressed by PTPRG-AS1 silencing. In contrast, cell apoptosis was promoted by loss of PTPRG-AS1. Regarding the mechanism, PTPRG-AS1 could serve as a competing endogenous RNA in EOC cells by decoying microRNA-545-3p (miR-545-3p), thereby elevating histone deacetylase 4 (HDAC4) expression. Furthermore, rescue experiments revealed that PTPRG-AS1 knockdown-mediated effects on EOC cells were, in part, counteracted by the inhibition of miR-545-3p or restoration of HDAC4.Conclusions: PTPRG-AS1 functioned as an oncogenic lncRNA that aggravated the malignancy of EOC through the miR-545-3p/HDAC4 ceRNA network. Thus, targeting the PTPRG-AS1/miR-545-3p/HDAC4 pathway may be a novel strategy for EOC anticancer therapy.

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Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway

Gene ◽

10.1016/j.gene.2018.04.014 ◽

2018 ◽

Vol 665 ◽

pp. 141-148 ◽

Cited By ~ 31

Author(s):

Ningning Sun ◽

Guozun Zhang ◽

Yingying Liu

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Cancer Progression ◽

Non Coding Rna ◽

Colon Cancer Progression ◽

Long Non Coding Rna

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Colon Cancer-Upregulated Long Non-Coding RNA lincDUSP Regulates Cell Cycle Genes and Potentiates Resistance to Apoptosis

Scientific Reports ◽

10.1038/s41598-018-25530-5 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 12

Author(s):

Megan E. Forrest ◽

Alina Saiakhova ◽

Lydia Beard ◽

David A. Buchner ◽

Peter C. Scacheri ◽

...

Keyword(s):

Cell Cycle ◽

Colon Cancer ◽

Cell Cycle Genes ◽

Non Coding Rna ◽

Long Non Coding Rna

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HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000490131 ◽

2018 ◽

Vol 47 (3) ◽

pp. 893-913 ◽

Cited By ~ 87

Author(s):

Qing Tang ◽

Swei Sunny Hann

Keyword(s):

Drug Resistance ◽

Human Cancer ◽

Critical Role ◽

Stem Cell Differentiation ◽

Human Diseases ◽

Biological Functions ◽

Protein Coding ◽

Non Coding Rna ◽

And Function ◽

Long Non Coding Rna

Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.

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