Elevated Expression of LINC02257 and LINC00659 in Breast Cancer is Associated with Poor Survival and Immune Cell Infiltration

Long Noncoding RNAs (lncRNAs) as Biomarkers of Prognosis in TNBC and Non-TNBC Breast Cancer Patients

This computational study identifies several candidate lncRNAs associated with clinical outcomes in breast cancer, which should be interpreted as preliminary candidates, which require future validation and functional studies to determine their biological roles and evaluate their potential as prognostic biomarkers.

LINC00673-V4 Promotes Colorectal Cancer Cell Proliferation by Interacting With FUS and Restoring the Expression of Hippo-YAP Target Genes.

BACKGROUND Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide; thus, understanding its molecular mechanisms is critical for developing novel therapeutic targets. Long non-coding RNAs (lncRNAs) play crucial isoform-specific roles in cancer. While oncogenic lncRNA LINC00673 is known to be involved in multiple malignancies and possesses five distinct transcript variants, the functional role of LINC00673-V4-a highly expressed transcript variant in CRC-remains largely unexplored. This study investigated how LINC00673-V4 drives CRC proliferation by modulating the Hippo-Yes-associated protein (Hippo-YAP) signaling pathway. METHODS Survival analysis was performed using the GSE39582 dataset to assess the prognostic value of LINC00673 in patients with CRC. The expression of LINC00673 transcript variants in CRC cell lines was detected by quantitative PCR. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays were used to assess cell proliferation upon LINC00673-V4 knockdown or overexpression. Western blotting and immunofluorescence staining were utilized to analyze the expression of Hippo-YAP target genes. To confirm the interaction between LINC00673-V4 and fused in sarcoma (FUS), RNA immunoprecipitation (RIP) was performed, while co-IP was used to investigate potential protein-protein interactions. RESULTS High LINC00673 expression was observed in CRC cell lines and was associated with a poor prognosis in patients with CRC. Among the five LINC00673 transcript variants, LINC00673-V3 and LINC00673-V4 were the predominantly expressed isoforms; however, only LINC00673-V4 significantly promoted CRC cell proliferation. LINC00673-V4 inhibited YAP phosphorylation at Ser127, promoted YAP nuclear translocation, and upregulated the expression of Hippo-YAP target genes (connective tissue growth factor, cysteine-rich angiogenic inducer 61, survivin). RIP assays confirmed an association between LINC00673-V4 and FUS, while co-immunoprecipitation (co-IP) assays revealed that FUS interacted with both YAP and large tumor suppressor 1 (LATS1), suggesting FUS may facilitate LATS1-mediated YAP phosphorylation. FUS was found to promote LATS1-mediated YAP Ser127 phosphorylation, induce YAP cytoplasmic retention, and down-regulate Hippo-YAP target gene expression. Rescue experiments showed that LINC00673-V4 reversed the FUS-induced suppression of Hippo-YAP target gene expression. CONCLUSIONS Our study identified LINC00673-V4 as an isoform-specific oncogenic lncRNA in CRC. By associating with FUS, LINC00673-V4 sequesters FUS away from the LATS1/YAP complex; thereby inhibiting FUS-mediated YAP phosphorylation and enhancing Hippo-YAP target gene expression. These findings expand the landscape of lncRNA isoform-specific regulation in cancer, highlighting LINC00673-V4 as a potential prognostic biomarker and therapeutic target for CRC.

SNP rs7430456 mediated LINC00578 drives triple negative breast cancer through regulating miR-143-5p expression

A large number of cancer-related single-nucleotide polymorphisms (SNPs) are distributed in the genomic regions of long non-coding RNAs (lncRNAs), yet the mechanisms linking them to cancer risk have not been fully clarified so far. This study explored LINC00578 rs7430456’s association with breast cancer susceptibility and LINC00578’s role/mechanism in triple-negative breast cancer (TNBC). A total of 480 breast cancer patients and 460 controls were enrolled. LINC00578 rs7430456 genotyping and LINC00578 expression detection via RT-qPCR were performed. Functional assays (proliferation, migration, invasion) were conducted in TNBC cell lines, and the LINC00578-miR-143-5p interaction was explored by dual-luciferase reporter assay. LINC00578 rs7430456 G allele and AG/GG genotypes reduced breast cancer risk. LINC00578 was upregulated in breast cancer (especially TNBC) with an AUC of 0.873 for diagnosis. LINC00578 knockdown inhibited TNBC cell proliferation, migration, and invasion. LINC00578 sponged miR-143-5p, and miR-143-5p mediated its oncogenic effects. LINC00578 rs7430456 is associated with breast cancer susceptibility, and LINC00578 promotes TNBC progression via sponging miR-143-5p, being a potential biomarker and therapeutic target for breast cancer, particularly TNBC.

C17orf75 (Njmu-R1) promotes hepatocellular carcinoma progression: a pan-cancer analysis and experimental validation

Background Chromosome 17 Open Reading Frame 75 (C17orf75) encodes the protein Njmu-R1 (Protein Njmu-R1),, which is involved in intracellular vesicle trafficking; however, its role in tumor progression remains largely unclear. Methods Public datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA) were analyzed to evaluate the expression profile, mutation landscape, and diagnostic and prognostic value of C17orf75. Bioinformatics analyses were subsequently performed to explore its associations with immune infiltration. In addition, functional assays were conducted on Hep3B and MHCC-97H cells, and immunohistochemistry (IHC) was performed on clinical liver hepatocellular carcinoma (LIHC) samples. Results C17orf75 was significantly upregulated in multiple cancer types, particularly in LIHC. Elevated C17orf75 expression was associated with unfavorable prognosis and advanced clinicopathological features in LIHC. Functional enrichment analyses indicated that C17orf75-related genes were involved in cell cycle regulation, DNA replication, and epithelial–mesenchymal transition (EMT). Furthermore, C17orf75 expression was closely correlated with immune infiltration, ferroptosis-related genes, and m6A regulators. Knockdown of C17orf75 inhibited the proliferation, migration, and invasion of LIHC cells. C17orf75 knockdown induced G2-phase arrest without significantly affecting apoptosis. Moreover, knockdown of C17orf75 suppressed EMT. Conclusion C17orf75 plays an important role in LIHC progression by regulating cell cycle progression and EMT, and it may serve as a potential therapeutic target for LIHC.

LINC00460 drives clear cell renal cell carcinoma progression via complement/coagulation and p53 pathways: a potential therapeutic target.

This study demonstrates that the long noncoding RNA (lncRNA) LINC00460 is significantly overexpressed in clear cell renal cell carcinoma (ccRCC) and is strongly associated with adverse clinical outcomes. Analysis of data from The Cancer Genome Atlas (TCGA), validated by an independent cohort (GSE53757) and quantitative real-time polymerase chain reaction (qRT-PCR), shows that high LINC00460 expression has robust diagnostic value (area under the curve [AUC] = 0.818) and predicts shorter overall survival, highlighting its potential as a prognostic biomarker. Functional enrichment analyses indicate that LINC00460 is involved in key pathways, including complement and coagulation cascades, cytokine-cytokine receptor interactions, extracellular matrix remodeling, and p53 signaling. In vitro experiments confirm that silencing LINC00460 in ccRCC cell lines (Caki-2 and ACHN) markedly inhibits tumor cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, LINC00460 knockdown reduces levels of inflammatory factors (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and C-X-C motif chemokine ligand 8 [CXCL8]) and coagulation-related proteins (C3, SERPINA1, and PLAU), and activates the p53 pathway by upregulating p21 and BAX while downregulating Bcl-2. Genomic analysis reveals higher mutation rates of BAP1 and LRP2 in LINC00460-high tumors, and drug repurposing screening identifies cinchonine and iproniazid as candidate therapeutic agents. These findings establish LINC00460 as an oncogenic driver in ccRCC and a promising target for both diagnosis and precision therapy.

LINC01133 knockout increases malignancy by migration mechanisms in Hs578T Triple-Negative Breast Cancer Cells