long non-coding rnas

We aimed to explore the prediction value of disulfidptosis-related long noncoding RNAs (lncRNAs) on the prognosis and immunotherapy efficiency of patients with head and neck squamous carcinoma (HNSCC).

Clinical and RNA-seq information were collected from The Cancer Genome Atlas (TCGA) and Genome Data Sharing (GDC) portal. The Pearson correlation analysis, univariate COX regression analysis, the least absolute shrinkage and selection operator (LASSO) COX regression were employed to construct the disulfidptosis-related lncRNAs (DRLs) prognostic model. The Kaplan-Meier survival curve, principal component analysis (PCA), receiver operating characteristic (ROC) curves and areas under the curves (AUCs) were used to examine the accuracy of the prognostic model. ssGSEA, mutation and functional and gene set enrichment analysis was performed to quantify the immune cell infiltration, immune function and functional enrichments. Finally, the mRNA expression of the DRLs was verified by real‑time PCR (RT-PCR) in HNSCC cells.

A new DRLs prognostic model (AC083967.1, AC106820.5, AC245041.2, AL590617.2, AP002478.1, and VPS9D1-AS1) with an independent prognostic value of HNSCC patients was successfully identified. In addition, the DRLs prognostic model was related with immune signature and drug therapy response. Meanwhile, the mRNA expression level of the 6 DRLs detected by RT-PCR was consistent with the results of bioinformatic analysis.

We developed a new DRLs prognostic model of HNSCC, which could effectively predicate the prognosis and therapy response of HNSCC patients and provide insights into personalized therapeutics.

Glioblastoma multiforme (GBM) is one of the most invasive types of brain cancer. LncRNAs can be considered a new prognostic and diagnostic biomarker in GBM. This study comprehensively explored the interaction of lncRNAs with mRNAs in the TCGA database and proposed a novel promising biomarker with favorable diagnostic and prognostic values.

The public data of RNA-seq and related clinical data were downloaded from the TCGA database. Differential expression analysis was conducted in R. GO and KEGG signaling pathways were used for enrichment. The STRING database was used for PPI analysis. CE-network was constructed by STAR database. Kaplan-Meier survival analysis and ROC curve analysis to indicate the biomarkers' diagnostic and prognostic values.

Differentially expressed data illustrated that 4428 mRNAs were differentially expressed in GBM. The GO and KEGG pathway analysis showed that the differentially expressed mRNAs were enriched in critical biological processes. The PPI showed that WEE1, BARD1, and CDK6 were the important PPI hubs. The ceRNA network data demonstrated critical lncRNAs. The data revealed that the lncRNA CRNDE, LINC00957, AC072061.1, AC068888.1, and DBH-AS1 are potential diagnostic prognostic biomarkers in the GBM patients.

Altogether, we demonstrated lncRNA, and mRNA interaction and mentioned regulatory networks, considered a therapeutic option in GBM. In addition, we proposed potential diagnostic and prognostic biomarkers for the patients.

Mycobacterium tuberculosis is the bacterium that causes tuberculosis. In this bacteria, long non-coding RNAs (lncRNA) can positively and negatively alter the expression of various genes through various mechanisms, such as activating transcription factors or binding to DNA targets of the chromatin complex. The  current study's purpose was to review the lncRNAs in M. tuberculosis.  The search was done with the keyword including lncRNAs, lncRNA, Long ncRNA, LincRNAs, Long ncRNA, long noncoding RNA, TB, Pulmonary Tuberculosis, Pulmonary TB, Mycobacterium tuberculosis in Pub Med, Web of Science Direct, Scopus, Scientific Information Databases, and Google scholar between 2000 and 2020. A total of 124 articles were found in PubMed,Science Direct, Scopus, Ovid,  Cochrane, and Google Scholar, of which 20  papers were selected from the databases. In revising the title and abstract, 84 articles were excluded from our study. Finally, 19 articles were included in our study, which included 4444 patients with tuberculosis. All studies were performed in China using the qRT-PCR method. The  present study's results showed an acceptable association between lncRNA and SNP with tuberculosis and M. tuberculosis. Also, these regulatory factors play an essential  role as diagnostic biomarkers and the development of new therapies.

Esophageal carcinoma (ESCA) is one of the most common types of cancer. ESCA accounted for the sixth leading cause of cancer-related deaths globally. Most patients are diagnosed at late stages of ESCA, with distance metastasis or chemoresistance, which leads to a poor prognosis. Previous studies demonstrated lncRNA presentation and roles in ESCA cells and patients' tissue. It has been proposed that lncRNAs can be considered a new prognostic and diagnostic biomarker in ESCA. In this study, we comprehensively explored the interaction of lncRNAs with miRNAs and mRNAs of the TCGA database and proposed a novel promising biomarker with good diagnostic and prognostic values.

The public data of RNA-seq, miR-seq, and related clinical data were downloaded from the TCGA database. Differential expression analysis was conducted by “limma” in R. GO, and KEGG signaling pathways were used for enrichments. STRING database was used for PPI analysis. CE-network was constructed by the STAR database in R. Kaplan-Meier survival analysis (log-rank test), and ROC curve analysis was used to indicate the diagnostic and prognostic values of the biomarkers.

Differentially expressed data illustrated that 45.8% of the total mRNAs in the data related to ESCA patients showed increased expression and 54.2% decreased expression. The GO and KEGG pathway analysis showed that the differentially expressed mRNAs were enriched in critical biological processes. Important protein-protein interaction hubs were identified. The ceRNA network data demonstrated critical lncRNAs essential in ESCA development, including TMEM16B-AS1, AC093010.3, SNHG3, and PVT1. The data revealed that the lncRNA WDFY3-AS2, AC108449.2, DLEU2, AC007128.1, and AP003356.1 are potential diagnostic and prognostic biomarkers in ESCA patients.

Altogether, this study demonstrates lncRNA, miRNA, and mRNA interaction and mentions regulatory networks which can be considered as a therapeutic option in ESCA. In addition, we proposed potential diagnostic and prognostic biomarkers for ESCA patients.

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies in the world with a high mortality rate, making screening and early detection of the condition essential. Long non-coding RNAs (lncRNAs) have a significant role in the initiation and advancement of numerous malignancies, including CRC, by taking part in the control of gene and protein expression that affects apoptosis, cell proliferation, and immunological responses. In this study, through bioinformatics methods, we investigated this non-coding group in CRC and the normal group in both early and advanced stages of the disease.

In order to identify the lncRNAs that could have a tumor-suppressing role in CRC, RNA sequencing data from the cancer genome atlas (TCGA) were analyzed. Then, the Pearson correlation test was applied between the expression level of candidate lncRNAs and all genes expressed for identifying potential pathway. Genes with the highest correlation were selected and subjected to gene enrichment analysis. Also, the roles of identified lncRNAs were evaluated in terms of biomarkers.

The results of the expression analysis for the TCGA data showed that the expression of the IRF1-AS1, LINC01871, TRG-AS1, and USP30-AS decreased during the progression (stages III and IV compared with stages I and II) of CRC. The enrichment results of all the genes in the co-expression network related to IRF1-AS1, LINC01871, TRG-AS1, and USP30-AS showed that these lncRNAs could play a role in immune response, inflammation, and IL-6/JAK/STAT3 signaling and apoptosis pathways. Additionally, our findings demonstrated that the aforesaid lncRNAs were significantly lower in CRC samples compared with normal samples based on TCGA data, Also, the expression of some of them may serve as an appropriate biomarker.

The results of this study showed that IRF1-AS1, LINC01871, TRG-AS1, and USP30-AS decreased during the progression of CRC and could play a tumor-suppressing role.

Studies show that chronic injuries like air pollution or acute damage such as hepatic ischemia-reperfusion (IR) cause various cellular pathologies such as oxidative stress, apoptosis, autophagy, and inflammation in hepatocytes. p-Coumaric acid (p-CA) is known as an antioxidant with many therapeutic impacts on inflammatory-related pathologies. In this experiment, we aimed to assess the hepatoprotective effects of p-CA on liver damage induced by dust and IR injury in adult male rats. 

Forty-eight adult male Wistar rats were divided into 6 groups; Control (CTRL); sham; DMSO+Dust+Laparotomy (LPT); DMSO+Dust+Ischemia-reperfusion (IR); p-CA+Dust+LPT; and p-CA+Dust+IR. Clean air, DMSO, p-CA, and dust were administrated 3 days a week for 6 consecutive weeks. Animals were sacrificed, the blood samples were aspirated and the liver sections were prepared for biochemical and histopathological assessments. 

Significantly (P<0.05), the results represented that dust and IR can potentially increase the levels of ALT, AST, direct and total bilirubin, triglyceride, and cholesterol in serum. Also, MDA, TNF-α, NF-κB, HMGB-1, and ATG-7 levels were increased in hepatocytes. Gene expression of Nrf2, HOX-1, IL-6, HOTAIR, and miR-34a showed an incremental trend in the liver tissue. Total antioxidant capacity (TAC) in hepatocytes was decreased following dust exposure and IR induction. Also, miR-20b-5p, MEG3, and SIRT1 in the liver were decreased in dust and dust+IR groups. 

p-CA alleviated pathological changes caused by dust exposure and IR injury. p-CA protected hepatic injury induced by dust and IR by inhibition of oxidative injury, inflammation, and autophagy.

Prostate cancer (PCa) is a common malignant disease with high mortality rates that develops and progresses in an androgen-dependent way. In recent years, RNA sequencing enabled identification of many PCa-related long noncoding RNAs including androgen receptor-regulated long non-coding RNA 1 (ARLNC1) and prostate cancer-associated transcript 1 (PCAT1). In the present study, our goal was to illuminate expression changes of ARLNC1 and PCAT1 in the context of androgen stimulation or androgen receptor (AR) blockade with respect to AR expression status. In this experimental study, LNCaP cells and higher AR-expressing LNCaP-AR++ cells were used as cell models. Cells were treated with dihydrotestosterone (DHT) as an androgen stimulator and/or enzalutamide as an AR inhibitor. Cell viability was assessed using annexin V and propidium iodide (PI) staining in flow cytometry. Androgen stimulation prompted baseline ARLNC1 levels by 53.5-fold in the LNCaP cells (P=0.01) and by 25-fold in the LNCAP-AR+ cells (P=0.18). AR inhibition by enzalutamide reduced baseline ARLNC1 in LNCaP-AR++ cells by 2-fold (P=0.01), but to a lesser extent in LNCaP cells. Co-treatment of cells with DHT and enzalutamide led to a remarkable decrease in the DHT effect on ARLNC1 expression. No specific effect of androgen stimulation or AR blockade on PCAT1 expression was detected. Our results revealed that the extent of induction of ARLNC1 by androgen is modulated by receptor expression status. In addition, we determined that AR blockade, via enzalutamide, effectively suppresses ARLNC1 both at baseline and after induction by DHT.

Colorectal cancer (CRC) has not only seriously affected people’s lives, but also burdened the government healthcare system. Long non-coding RNAs (lncRNA) have attracted more and more attention in the cancer study field.

Experiments were completed in the Medical Research and Innovation Center of Shanghai Pudong Hospital, China from 2019 to 2020. Cell cycle was detected by western blot analyzing and flow cytometry. Apoptosis analysis were determined using flow cytometry or western blot analysis. LncRNA CKMT2-AS1 was knocked down by shRNA transfection.

We found CKMT2-AS1 was the most significant=0.0105 for SW480 and P=0.0071 for HCT116) difference lncRNA between colorectal cancer treated with autophagy inducer and colorectal cancer without any treatment. Effective shRNA-CKMT2-AS1 was also designed. Following, we found the treatment of autophagy inducer and autophagy inducer + shRNA-NC were able to suppress the proliferation of both SW480 and HCT116 cells. In addition, the treatment of autophagy inducer + shRNA-CKMT2-AS1 significantly reduced the apoptosis of SW480 and HCT116 cells induced by autophagy. Furthermore, we found the phosphorylation of mTOR, AKT was enhanced in SW480, and HCT116 cells treated with autophagy inducer + shRNA-CKMT2-AS1 compared to the cells treated with autophagy inducer of autophagy inducer + shRNA-NC.

Enhancing the expression of CKMT2-AS1 will become a promising strategy to prevent the progress of colorectal cancer.

Colorectal cancer (CRC), like other cancers, needs faster and more accurate identifications. A well-timed prognosis of CRC could be an important turning point in the survival of patients. Supplementary signs, such as long non-coding RNAs (lncRNAs), could be helpful for this purpose. A new possible biomarker for CRC identification is introduced by this study.

 RNA extraction was performed by the RNX-Plus solution for 64 tumor and non-tumor tissues. Complementary DNAs (cDNAs) were synthesized, and quantitative real-time PCR was performed for relative expression level measurement and the data was analyzed statistically using the Prism 6 software. For Small nucleolar host gene 6 knockdown, siRNA was designed based on Reynolds rules. The cells were cultured in their appropriate media, and the siRNA-lipofectamine complex was formed. The transfection complex was presented for sw48, sw480, and sw1116 as CRC cells with different grades. After transfection, the SNHG6/β actin ratio was determined. Then, the distribution of siRNA-treated cells was determined by the Partec flow cytometer instrument and analyzed by the FloMax software.

SNHG6 was more expressed in CRC tumors than non-tumor tissues. In tumor tissues, SNHG6 upregulation and tumors’ grade progression were concurrent. SNHG6 was upregulated in cases with lymphovascular invasion than in cases with perineural invasion. The knockdown of SNHG6 conduced to G1 arrest in CRC cells, more noticeably in high-grade ones.

SNHG6 could be applied as a consideration to differentiate tumor and non-tumor tissues and grade definition in colorectal malignancies, and it could participate in colorectal tumor formation as a cell cycle progressive factor.

Long non-coding RNAs (lncRNAs) associated with various cancers, including colorectal cancer (CRC), could be collected from body fluids easily. Our aims were to determine the expression level of HOTTIP lncRNA in plasma samples of healthy individuals and CRC patients as well as their relationship with clinico-pathological characteristics of patients. First, total RNA was extracted from the plasma samples of 100 subjects including 50 patients and 50 age and sex matched healthy persons. Then, gene expression was measured using real-time PCR technique. The sensitivity and specificity of HOTTIP dysregulation in CRC and healthy individual’s plasma was measured by receiver operating characteristic (ROC) analysis. As compared with healthy controls, HOTTIP lncRNA was over expressed in a statistically significant manner in plasma samples of patients (P = 0.001). Significant relationship between HOTTIP expression and positive family history of CRC was observed, too (P = 0.04). The ROC curve analysis showed an AUC value of 0.775, a specificity of 82%, a sensitivity of 76%, with a cut off value equal to 2.40 (P = 0.001). HOTTIP transcript can be proposed as a new biomarker for early diagnosis due to the increased expression in plasma samples of patients with CRC and the relatively high sensitivity and specificity.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the long non-coding RNAs that plays an important role in invasion, cell proliferation and metastasis of various cancers. However, insufficient information on the association of MALAT1 with the methylation process and its role in the development of colorectal cancer is not yet fully available. This study set out to determine the effect of methylation on MALAT1 gene in primary colorectal lesions and tumors to gain further knowledge about the diagnostic and prognostic value of MALAT1.

Methylation Pattern of MALAT1 promoter determined by Methylation-Specific Polymerase Chain Reaction (MSP) in 86 colorectal primary lesions, tumors and normal specimens. MALAT1 methylation pattern was compared in tumor and polyp tissue. In order to obtain more accurate results, we investigated the association of MALAT1 promoter methylation pattern with clinicopathologic factors in patients.

The results indicated that the MALAT1 promoter methylation pattern in tumor tissue, primary lesions tissue and normal was not significant difference (p=0.430). Moreover, compared, the MALAT1 promoter methylation pattern between polyp types and tumor tissue groups was not significant (p=0.437). Surprisingly, the methylation frequency of MALAT1 methylation was significantly higher in colon lesions in comparison with their rectum lesion, p = 0.035. In addition, significant hypermethylation of MALAT1 was not observed between the other patients’ clinicopathological data at both polyps 46/66 and tumor tissue 20/66.

This study suggests that the MALAT1 promoter methylation pattern in patients with colorectal primary lesions and tumors compared with normal tissue as not a significant risk factor for colorectal cancer. Moreover, clearance the significantly higher methylation frequency in colon lesions in comparison with their rectum lesion need to be further explored.

As the second cause of cancer death, gastric cancer (GC) is one of the eminent dilemmas all over the world, therefore investigating the molecular mechanisms involved in this cancer is pivotal. Unrestricted proliferation is one of the characteristics of cancerous cells, which is due to deficiency in cell regulatory systems. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the epigenome. lncRNA extra coding CEBPA (ecCEBPA) is involved in DNA methylation. This lncRNA reduces CEBPA promoter methylation by interacting with DNA methyltransferase 1. lncRNA UCA1 (urothelial carcinoma-associated 1) elevates cell proliferation through the PI3K/Akt signaling pathway which has a critical role in cell growth and apoptosis. The aim of this study was to examine the expression of ecCEBPA and UCA1 genes in GC tissues as well as their clinical significance.
Total RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed for cells and 80 paired GC tissues. Furthermore, clinical relevance of UCA1 expression was investigated in TCGA cohort data.
Our results showed ecCEBPA and UCA1 over-expression in GC tissues. Furthermore, lncRNAs associations with clinicopathological features were demonstrated both in the current and TCGA cohort. Kaplan-Meier analysis indicated that patients with higher UCA1 expression had a worse overall survival in the case of pancreatic and lung adenocarcinomas but not other solid cancer types including GC.
These data demonstrate UCA1 and ecCEBPA involvement in GC and suggest that these lncRNAs might be useful as diagnostic/ prognostic biomarkers in cancer.