LINC01446/miR-338-3p/APEX1 Axis Promotes Ferroptosis Defense and Progression in Esophageal Squamous Cell Carcinoma

LncRNA DLGAP1-AS2 promotes ESCC progression and indicates unfavorable prognosis via the miR-101-3p/EZH2 axis

LncRNAs are crucial regulators and biomarkers in various cancers. However, their expression and functions in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. This study explored the clinial relevance and mechanisms of LncRNA DLGAP1-AS2 in ESCC. Utilizing the GEO dataset, the identification of differentially expressed lncRNAs in ESCC encompassed DLGAP1-AS2. RT-qPCR was employed to measure its expression in 135 paired tumors and adjacent non-cancerous tissue samples. Patients were followed up for five years. Kaplan-Meier curves and Cox regression analysis evaluated DLGAP1-AS2’s prognostic impact, while CCK-8 and Transwell assays assessed cell proliferation. Additionally, commercial assay kits measured ROS, MDA, GSH, and iron levels. DLR and RIP assays confirmed miR-101-3p targeting DLGAP1-AS2 and EZH2. DLGAP1-AS2 was markedly upregulated in ESCC tumor tissues and cell lines. High expression of DLGAP1-AS2 correlated with advanced clinical stages and extensive lymph node metastasis in ESCC patients, and patients with elevated DLGAP1-AS2 expression had a worse prognosis. Mechanistically, DLGAP1-AS2 competitively binds miR-101-3p, upregulating EZH2. Depleting DLGAP1-AS2 significantly curbed ESCC cell proliferation, migration, invasion, and EMT, while boosting ferroptosis—an effect notably reversed by miR-101-3p reduction. DLGAP1-AS2 acts as a potential biomarker for unfavorable prognosis in ESCC patients. Mechanistically, it promotes malignant phenotypes of ESCC cells in vitro by regulating the miR-101-3p/EZH2 axis, enhancing proliferation and EMT, while suppressing ferroptosis.

The ferroptosis-related LncRNA CASC9 reveals its potential as a diagnostic and prognostic biomarker in esophageal squamous cell carcinoma.

This study aimed to investigate the role of ferroptosis-related long non-coding RNA CASC9 in the carcinogenic process of esophageal squamous cell carcinoma and evaluate its clinical diagnostic and prognostic value. LncRNA microarray screening was performed to identify differentially expressed genes in ESCC tissues. CASC9 expression was validated in 150 paired ESCC tissues, precancerous lesions, and cell lines by qRT-PCR. The correlation between CASC9 expression and clinicopathological characteristics as well as survival outcomes was analyzed. In vitro functional assays were conducted to examine the effects of CASC9 on ESCC cell proliferation, apoptosis, invasion, and migration. The role of CASC9 in ferroptosis was explored by detecting GSH, MDA, and ROS levels. CASC9 was significantly overexpressed in 92.7% of ESCC tissues (mean 11-fold upregulation), showing stepwise elevation during disease progression (normal mucosa→LGIN→HGIN→invasive carcinoma); High CASC9 expression correlated significantly with depth of invasion (P = 0.001) and clinical stage (P = 0.033), serving as an independent risk factor for overall survival (HR = 1.550, P = 0.026); Plasma CASC9 levels were significantly elevated in ESCC patients and markedly decreased at 14 and 30 days postoperatively. CASC9 knockdown markedly suppressed ESCC cell proliferation, invasion, and migration while promoting apoptosis. Reduced GSH and MDA/ROS accumulation indicate that CASC9 regulates ESCC progression via the ferroptosis pathway. In combination with clinicopathological features, a nomogram based on the gene signature presented strong predictive power and risk stratification for ESCC. CASC9 functions as an oncogenic lncRNA that promotes ESCC progression by modulating ferroptosis, representing a promising early diagnostic biomarker, prognostic predictor, and therapeutic target.

Integrative Pan‐Cancer Characterization of lncRNA UPK1A‐AS1 and Its Role in Hypoxia‐Associated Sorafenib Resistance in Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer‐associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype‐Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy‐number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type‐dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia‐inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type‐dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia‐associated drug resistance in HCC.

ATP7A Orchestrates Tumor Progression and Cuproptosis in Hepatocellular Carcinoma via the LINC02038‐miR‐506‐3p Regulatory Circuit

It is revealed that the LINC02038/miR‐506‐3p/ATP7A axis played a crucial oncogenic role in HCC by driving tumor progression and modulating cuproptosis, and represents a promising prognostic biomarker and a potential therapeutic target for HCC intervention.

KAT2B epigenetically activates GSTZ1 via H3K9ac to suppress proliferation and stemness and enhance ferroptosis in oral squamous cell carcinoma.

The lncRNA SOX2OT Drives Non-Small Cell Lung Cancer Progression and Metastasis by Suppressing miR-143

In terms of cancer-related death, non-small cell lung cancer (NSCLC), the world’s leading cause, highlights the need for continued research into the genetic factors that influence tumor growth. Long non-coding RNAs (lncRNAs) are now well recognized as essential regulators of oncogenic signaling cascades; nevertheless, the specific role and molecular basis of the SOX2 overlapping transcript (SOX2OT) in NSCLC are not entirely understood. This study examined the functional importance of SOX2OT and its regulatory interactions with tumor-suppressive microRNAs in NSCLC cells. In A549 and Calu-3 cells, RNA interference-mediated SOX2OT silencing dramatically reduced cellular proliferation, migration, and invasiveness. Moreover, SOX2OT knockdown was associated with inhibition of epithelial–mesenchymal transition (EMT), alongside induction of cell cycle arrest and activation of apoptotic pathways. Integrated transcriptomic profiling and bioinformatic prediction analyses identified miR-143 as a putative downstream effector of SOX2OT activity. Consistently, depletion of SOX2OT resulted in marked elevation of miR-143 expression, which corresponded with downregulation of oncogenic mediators, including STAT3, EZH2, and CXCL13. As a result of SOX2OT suppression, both the transcript and the protein levels of PTEN were restored. Further functional characterization demonstrated that SOX2OT knockdown inhibits EMT progression by decreasing mesenchymal markers and EMT-related transcription factors (TFs) while concomitantly enhancing epithelial marker expression. Collectively, these findings suggest that SOX2OT contributes to NSCLC pathogenesis through regulation of a miR-143-centered signaling network that influences oncogenic signaling, cellular survival, and metastatic potential. Targeting the SOX2OT/miR-143 regulatory axis may therefore represent a promising therapeutic approach for NSCLC, while also underscoring the broader importance of lncRNA-mediated post-transcriptional regulation in lung cancer biology.