systemic-immune-inflammatory-index-for-evaluating-robotic

Systemic Immune-Inflammatory Index For Evaluating Robotic and Laparoscopic Proximal Gastrectomy in Upper Gastric Cancer

Tumor resection is a commonly used treatment method in clinical practice. With the increasing refinement of tumor surgery, the application of ...

The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University

Long non-coding RNAs (lncRNAs) play important roles in a range of different human cancers. However, the role of lncRNA solute carrier organic anion transporter family member 4A1-AS1 (SLCO4A1-AS1) in colon cancer remains enigmatic. Hence, we aimed to explore the specific role of SLCO4A1-AS1 in colon cancer stem cells. Colon cancer-related differentially expressed lncRNA and mRNA were screened using microarray-based analysis, and the expression of SLCO4A1-AS1 and SLCO4A1 in colon cancer tissues was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. The interaction among SLCO4A1-AS1, microRNA-150-3p (miR-150-3p) and SLCO4A1 was verified using dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Moreover, SLCO4A1-AS1, miR-150-3p and/or SLCO4A1 were overexpressed or depleted in colon cancer cells to detect their effects on migration, invasion, sphere formation, apoptosis and tumorigenesis abilities of colon cancer stem CD133CD44 cells using both in vitro and in vivo assays. SLCO4A1-AS1 and SLCO4A1 were screened as the differentially expressed lncRNA and mRNA in colon cancer tissues. SLCO4A1-AS1 was confirmed to competitively bind to miR-150-3p to elevate SLCO4A1 expression. Moreover, knockdown of SLCO4A1-AS1 decreased SLCO4A1 expression, thus inhibiting cell migration, invasion, sphere formation, and tumorigenesis abilities and enhancing the apoptosis of CD133CD44 cells. Collectively, these findings provide evidence demonstrating that depleting SLCO4A1-AS1 competitively binds to miR-150-3p, which downregulates SLCO4A1 expression, thus hindering colon cancer progression.

LncRNA SLCO4A1-AS1 modulates colon cancer stem cell properties by binding to miR-150-3p and positively regulating SLCO4A1.

The purpose of our investigation is to explore the putative molecular mechanisms underpinning LINC00858 involvement in colon cancer. The expression of LINC00858 in TCGA data was identified using the GEPIA website. Colon cancer cancerous tissues were clinically collected. The expression of LINC00858, RAD21, and PCNP in colon tissues or cells was determined using RT-qPCR. The interactions among LINC00858, RAD21, and PCNP promoter region were determined by means of RNA pull down, RIP, and ChIP assays. Cell proliferative, apoptotic, invasive, and migrated capabilities were evaluated. Western blot was conducted to determine RAD21, PCNP, phosphorylated (p)-STAT3, STAT3, p-STAT5 and STAT5 and apoptosis related proteins. A nude mouse model of colon cancer was constructed and tumorigenesis of colon cancer cells was observed. LINC00858 was upregulated in cancerous tissues and cells. LINC00858 recruited the transcription factor RAD21. Overexpression of LINC00858 promoted the binding of RAD21 and PCNP promoter region, which increased the expression of PCNP. Silencing of RAD21 or PCNP reversed the promoting effect of LINC00858 on the disease initiation and development. PCNP silencing inhibited proliferative ability and promoted apoptotic ability of cancerous cells via STAT3/5 inhibition, which was reversed by colivelin-activated STAT3. In vivo experiments further verified that LINC00858 enhanced the tumorigenicity of colon cancer cells in vivo by regulating the RAD21/PCNP/STAT3/5 axis. It indicated the promoting role of LINC00858 in colon cancer progression though activating PCNP-mediated STAT3/5 pathway by recruiting RAD21.

LINC00858 promotes colon cancer progression through activation of STAT3/5 signaling by recruiting transcription factor RAD21 to upregulate PCNP.

COL12A1, a collagen type XII alpha 1 chain, has an instrumental role in the extracellular matrix (ECM), but its effect on gastric cancer (GC) and clinical significance remain unclear. In this study, co-expressed differentially expressed genes (co-DEGs) were identified using Venn diagrams based on datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) for gastric cancer RNA sequencing. Intersections between co-DEGs and TCGA prognosis-related genes were used to pinpoint genes that were differentially associated with prognosis. COL12A1 emerged as a key candidate gene. We analyzed COL12A1 expression in human GC tissues and explored its association with various clinicopathological parameters. Survival analysis, including overall survival (OS) and disease-free survival (DFS), was conducted using TCGA data, and a prognostic nomogram was constructed. The relative protein-encoding gene expression was assessed via immunohistochemistry (IHC) analysis of four downloaded datasets, along with PCR experiments. COL12A1-related DEGs were further identified using the LinkedOmics database, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Multiple databases were analysed for the relationship between COL12A1 and methylation. Immune cell infiltration was evaluated through CIBERSORT and TIMER databases, revealing a strong correlation between COL12A1 expression and immune cell presence in the tumor microenvironment. Single-cell expression analysis using TISCH provided further insights into the cellular context of COL12A1 expression. TISCH was used to analyse the single-cell expression of COL12A1. Finally, this work examined the correlation of COL12A1 with drug sensitivity via the RNAactDrug database. COL12A1 overexpression in gastric cancer was detected and foundto be closely related to clinicopathological features. GO/KEGG functional enrichment analysis revealed that COL12A1 was associated with pathways such as extracellular structure organization, extracellular matrix organization and the collagen-containing extracellular matrix. Analysis of several databases revealed that COL12A1 was associated with gene mutation and methylation. Additionally, as revealed by CIBERSORT profiling and TIMER database analysis, COL12A1 expression is related to immune cell infiltration. Correlation analysis via the RNAactDrug website revealed that COL12A1 is associated with drug sensitivity. In conclusion, COL12A1 is significantly overexpressed in gastric cancer and is associated with tumor progression, immune infiltration, and drug sensitivity. These findings suggest that COL12A1 may serve as a potential diagnostic and therapeutic biomarker for gastric cancer.

Multiomics analysis of COL12A1 as a promising prognostic biomarker for immune-related treatment of gastric cancer.

Gastric cancer (GC) is a common digestive tract cancer whose high heterogeneity and invasiveness lead to a low survival rate. Therefore, it is necessary to explore the potential molecular mechanism of GC.

Article	Year
LncRNA SLCO4A1-AS1 modulates colon cancer stem cell properties by binding to miR-150-3p and positively regulating SLCO4A1. Laboratory investigation; a journal of technical methods and pathology\| PubMed ID: 33958701	2021
LINC00858 promotes colon cancer progression through activation of STAT3/5 signaling by recruiting transcription factor RAD21 to upregulate PCNP. Cell death discovery\| PubMed ID: 35468892	2022
Multiomics analysis of COL12A1 as a promising prognostic biomarker for immune-related treatment of gastric cancer. Discover oncology\| PubMed ID: 41085846	2025
Collagen type I alpha 2 acts as a potential diagnostic biomarker and therapeutic targets for the prognosis in gastric cancer. Discover oncology\| PubMed ID: 41917621	2026

Xudong Song

Biography

JoVE Journal Publications

Other Publications