Non-coding RNAs are involved in tumor cell death and affect tumorigenesis, progression, and treatment: a systematic review.

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.

circMSH3 is a potential biomarker for the diagnosis of colorectal cancer and affects the distant metastasis of colorectal cancer.

Objectives: To identify the most significantly differentially expressed circular RNAs (circRNAs) in colorectal cancer (CRC) tissues in terms of their expression levels and circularity, and to analyze the relationship between their expression levels and the clinical characteristics of patients. Methods: circRNA RNA-seq technology was used to screen differentially expressed circRNAs in CRC. Sanger sequencing was used to identify circRNA back-splice junction sites. The relative expression levels of hsa_circ_0003761 (circMSH3) in CRC tissues and cell lines were detected by quantitative real-time fluorescence PCR technology. An RNA-protein pull-down assay was used to detect protein binding to circRNAs. Dual-luciferase reporter gene vectors were constructed to verify that circRNAs bind to microRNAs. Results: Four hundred twenty circRNAs were found to be upregulated, and 616 circRNAs were downregulated. circMSH3 was derived from the MutS homolog 3 (MSH3) gene and was formed by a loop of exons 9, 10, 11, and 12. In 110 pairs of CRC and adjacent tissues, circMSH3 expression was 4.487-fold higher in CRC tissues. circMSH3 was also highly expressed in the HT-29 and LOVO CRC cell lines. The expression level of circMSH3 was associated with distant metastasis in CRC patients (P = 0.043); the area under the curve (AUC) of circMSH3 for CRC diagnosis was 0.75, with a sensitivity and specificity of 70.9% and 66.4%, respectively. circMSH3 could bind to a variety of proteins, mainly those involved in RNA transcription, splicing, cell cycle, and cell junctions. Furthermore, circMSH3 could bind to miR-1276, miR-942-5p, and miR-409-3p. Conclusion: circMSH3 is a potential biomarker for the diagnosis of CRC and affects the distant metastasis of CRC. Multiple RNA-binding protein binds to circMSH3, and circMSH3 binds to miR-1276, miR-942-5p, and miR-409-3p, thereby affecting the expression of circMSH3.

Progress in research on tumor microenvironment-based spatial omics technologies.

Spatial omics technology integrates the concept of space into omics research and retains the spatial information of tissues or organs while obtaining molecular information. It is characterized by the ability to visualize changes in molecular information and yields intuitive and vivid visual results. Spatial omics technologies include spatial transcriptomics, spatial proteomics, spatial metabolomics, and other technologies, the most widely used of which are spatial transcriptomics and spatial proteomics. The tumor microenvironment refers to the surrounding microenvironment in which tumor cells exist, including the surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, various signaling molecules, and extracellular matrix. A key issue in modern tumor biology is the application of spatial omics to the study of the tumor microenvironment, which can reveal problems that conventional research techniques cannot, potentially leading to the development of novel therapeutic agents for cancer. This paper summarizes the progress of research on spatial transcriptomics and spatial proteomics technologies for characterizing the tumor immune microenvironment.

Downregulated miRNA-491-3p accelerates colorectal cancer growth by increasing uMtCK expression.

Colorectal carcinoma (CRC) is the second most frequent cancer worldwide. MiR-491-3p, a tumor-suppressive microRNA (miRNA, miR), has been revealed to be abnormally expressed in CRC tissues. Meanwhile, up-regulated ubiquitous mitochondrial creatine kinase (uMtCK) contributes to CRC cell proliferation. Here we aim to explore whether aberrant miR-491-3p expression promotes CRC progression through regulating uMtCK. To this end, miR-491-3p and uMtCK levels were assessed in CRC tissues using quantitative real-time PCR (qRT-PCR). The biological roles of miR-491-3p and uMtCK in regulating CRC growth were evaluated using colony formation assay and mouse Xenograft tumour model. We found that miR-491-3p expression was decreased in CRC tissues compared with matched para-cancerous tissues, whereas uMtCK expression was increased. Functionally, miR-491-3p overexpression repressed SW480 cell growth, whereas miR-491-3p depletion accelerated SW620 cell proliferation and growth. Inversely, uMtCK positively regulated CRC cell proliferation. Mechanistically, miR-491-3p post-transcriptionally downregulated uMtCK expression by binding to 3'-UTR of uMtCK. Consequently, restoring uMtCK expression markedly eliminated the role of miR-491-3p in suppressing CRC growth. Collectively, miR-491-3p functions as a tumour suppressor gene by repressing uMtCK, and may be a potential target for CRC treatment.

Septin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer.

BACKGROUND: Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. METHODS: We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). RESULTS: Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). CONCLUSION: Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.

Establishment and validation of a prognostic model based on HRR-related lncRNAs in colon adenocarcinoma.

BACKGROUND: Colon cancer (CRC) is the second leading cause of cancer-related death, and its 5-year survival rate is very low. Homologous recombination repair (HRR) is deficient in most colon cancer. Some long non-coding RNAs (lncRNAs) participate in tumorigenesis of colon cancer through the HRR pathway. We aim to establish a prognostic model based on the HRR-related lncRNAs, expecting to provide a new strategy for precision treatment development in colon cancer. METHODS: Pearson's correlation was used to identify the HRR-related prognostic lncRNAs in the TCGA-COAD cohort. The TCGA-COAD cohort was randomized into the training set and the testing set. LASSO Cox regression was used to establish the model which was analyzed in the training set and validated in the testing set and the entire TCGA-COAD cohort. Finally, we explored the potential biological function of our model. RESULTS: A prognostic model was established based on nineteen HRR-related lncRNAs in the training set. COAD patients were scored by the uniform formula and divided into high-risk and low-risk groups based on the median risk score. Patients with high-risk scores indicated poor prognosis in the training set, and the result was confirmed in the testing set and the entire TCGA-COAD cohort (all p < 0.01). Multivariable analysis suggested that our model was an independent factor for overall survival in COAD. The area under the curve (AUC) and C-index indicated that our model had better predictive efficiency than other indicators in the TCGA-COAD cohort. Functional enrichment analysis suggested that our model was associated with the MAPK pathway in COAD. Besides, our model was positively correlated with the HRD scores. CONCLUSION: A new prognostic model was established based on nineteen HRR-related lncRNAs which had excellent predictive efficiency on the prognosis of COAD. This prognostic model may provide a new strategy for prognostic prediction of COAD patients.

The Prognostic Value of a Tumor Microenvironment-Based Immune Cell Infiltration Score Model in Colon Cancer.

The current study aimed to construct a prognostic predictive model based on tumor microenvironment. CIBERSORT and ESTIMATE algorithms were used to reveal the immune cell infiltration (ICI) landscape of colon cancer. Patients were classified into three clusters by ConsensusClusterPlus algorithm. ICI scores of each patient were determined by principal component analysis. Patients were divided into high and low ICI score groups. Survival, gene expression, and somatic mutation of the two groups were compared. We found that patients with no lymph node invasion, no metastasis, T1-2 disease, and stage I-II had higher ICI scores. Calcium signaling pathway, leukocyte transendothelial migration pathway, MAPK signaling pathway, TGF ß pathway, and Wnt signaling pathway were enriched in the high ICI score group. Immune-checkpoint and immune-activity associated genes were decreased in high ICI score patients. Patients in the high ICI score group had better survival. Prognostic value of ICI score was independent of tumor mutational burden (TMB). The ICI score model constructed in the current study may serve as an independent prognostic biomarker in colon cancer.

Prognostic value of the NLR combined with CIP2A in the serum of patients with colorectal cancer.

OBJECTIVE: This study aimed to investigate the prognostic value of CIP2A (cancerous inhibitor of protein phosphatase 2A) and the NLR (neutrophil-lymphocyte ratio) in the serum of patients with CRC (colorectal cancer) after resection. METHODS: The clinicopathological data of 61 patients who underwent resection between January 2012 and December 2013 were collected. The NLR and CIP2A were divided into low score groups (0) and high score groups (1) with 2.03 and 6.07 as the optimal cut-off value according to the receiver operating characteristic (ROC) curve analysis. To identify the COCN (combination of CIP2A and the NLR) score, we added CIP2A and NLR points together and categorized CRC patients into three groups. Kaplan-Meier curves were used to identify the overall survival (OS) rates of the different groups. Finally, a ROC curve was plotted to evaluate the prognostic efficacy of COCN. RESULTS: The CIP2A was associated with location (P = 0.046) and CEA (P = 0.037) in patients with CRC. Kaplan-Meier survival curves showed that the 5-year OS of patients with low level of serum CIP2A was better than that of high level. The 5-year OS of the patients in the low NLR group was better than that of those in the high NLR group. The COCN score was associated with CEA (P < 0.001) and CA19-9 (P = 0.001). The 5-year OS of the patients in the COCN 0 group was highest, followed by that of those in the COCN 1 and COCN 2 groups. Age, N stage and M stage were factors associated with 5-year OS according to the univariate and multivariate analyses (P < 0.05). The area under the curve (AUC) for COCN was largest, indicating that COCN has better prognostic power than CIP2A or the NLR alone. CONCLUSION: COCN could be used as a better prognostic biomarker for CRC than the NLR or CIP2A alone.

[Acute Stanford B aortic intramural hematoma: early and midterm follow-ups and morphological changes of computed tomography].

OBJECTIVE: To summarize the clinical performances and analyze the morphological characters of acute Stanford B aortic intramural hematoma (IMH) on computed tomography (CT). METHODS: From January 2010 to June 2012, a total of 28 IMH patients at General Hospital of People's Liberation Army were retrospectively reviewed. Among them, 18 patients were followed up with CT. The data of vessel wall maximum thickness (MT), aortic maximum outside diameter (OD) and aortic inner diameter (ID) at onset and 1 week, 1, 3, 6, 12 months post-onset. Statistical analysis was performed with paired t-test. RESULTS: No mortality occurred. Two patients received endovascular repair. According to the follow-ups of 18 IMH patients, MT was (12.1 ± 2.6) mm on CT. Hematoma disappeared in 44.4% patients at 6 months post-onset. Hematoma disappeared more in the patients with MT ≤ 10 mm than those with > 10 mm (85.7% vs 18.2%, P < 0.01). Hematoma disappeared in 13/15 patients (86.7%) at 12 months post-onset. OD decreased (7.3 ± 2.4) mm per year and (6.7 ± 3.5) and (0.6 ± 1.7) mm within the first 6 months and 6 months later respectively. OD increased (0.9 ± 0.5) mm after the disappearance of hematoma. ID increased (6.1 ± 2.3) mm per year and (4.7 ± 1.8) and (1.2 ± 1.0) mm within the first 6 months and 6 months later respectively. CONCLUSION: The early and midterm outcomes of IHM are satisfactory most of hematoma disappear 12 months after onset. Hematoma disappears more rapidly in the patients with MT ≤ 10 mm than those with > 10 mm. OD reduces and ID increases before the disappearance of hematoma, and both increase afterward. Aortic cavity has a trend of dilating continually.