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Secondary trastuzumab resistance represents an evolutionary adaptation of HER2‐positive breast cancer during anti‐HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their associated genetic and epigenetic mechanisms. Here, transcriptome data is not only characterized but also examined epigenomic and 3D genome architecture information in both trastuzumab‐sensitive and secondary‐resistant breast cancer cells. The findings reveal that the global metabolic reprogramming associated with trastuzumab resistance may stem from genome‐wide alterations in both histone modifications and chromatin structure. Specifically, the transcriptional activities of key genes involved in lipid metabolism appear to be regulated by variant promoter H3K27me3 and H3K4me3 modifications, as well as promoter‐enhancer interactions. These discoveries offer valuable insights into how cancer cells adapt to anti‐tumor drugs and have the potential to impact future diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

In this study, we explored expression and functions of circular RNA LPAR3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC). The differential expression of circular RNAs (circRNAs) in 10 ESCC and corresponding paracarcinoma tissues was analyzed through circRNA microarray, then the candidate circRNAs were detected and verified through quantitative RT‐PCR, and a novel circRNA was screened, which was circLPAR3. Circular RNA LPAR3 showed apparently high expression in ESCC tissues and cells, which was closely correlated with the clinical stage and lymph node metastasis of ESCC patients. Circular RNA LPAR3 was mainly located in the cytoplasm of ESCC cells, which was more stable than the baseline gene. Circular RNA LPAR3 upregulated MET gene expression through sponge adsorption of microRNA (miR)‐198, activated the RAS/MAPK and the PI3K/Akt pathways, and promoted ESCC cell migration, invasion, and metastasis in vivo and in vitro. However, it had no effect on ESCC cell proliferation. Circular RNA LPAR3 can regulate the miR‐198‐MET signal axis to promote the migration, invasion, and metastasis of esophageal cancer cells, which can thereby serve as a potential diagnostic and therapeutic target of esophageal cancer. [ABSTRACT FROM AUTHOR]

MicroRNA‐1204 (miR‐1204), a member of the PVT1 region, may improve B cell differentiation and metastasis in breast cancer. However, the role of miR‐1204 in non‐small‐cell lung cancer (NSCLC) and its mechanism remain unclear. The GEO public database was first employed to find differentially expressed genes. The expression level of miR‐1204 in patient tissues and NSCLC cell lines was determined using qRT‐PCR. Cell proliferation assays were performed to investigate the impact of miR‐1204 on cell growth. Bioinformatics analysis and dual‐luciferase reporter assays were conducted to find potential target genes. Finally, we performed in vivo experiments to identify the effect of miR‐1204 on tumor formation in nude mice. It was first found that miR‐1204 was overexpressed in NSCLC tissues and cells. miR‐1204 increased the proliferation of NSCLC cells and reduced cell cycle arrest in vitro. PITX1 (paired like homeodomain 1) was found as a potential target gene. In addition, PITX1 was also found to be low in expression in NSCLC tissues and cells. To show that PITX1 reversed the function of miR‐1204 in promoting proliferation, confirmatory experiments were performed. Moreover, high miR‐1204 and low PITX1 expression was highly correlated with tumor size, lymph node metastasis, and the TNM stage in patients diagnosed with NSCLC. Our results suggested that upregulated miR‐1204 in NSCLC is associated with NSCLC progression and promotes NSCLC cell proliferation by downregulating PITX1. miR‐1204 may act as a poor prognostic factor and a potential therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

Objectives: Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR‐1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR‐1258 in non‐small‐cell lung cancer remains unclear. Methods: The differential expression of miR‐1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT‐PCR and ISH. Flow cytometry and CCK‐8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR‐1258. Potential targets of miR‐1258 were verified by dual luciferase reporter assay, qRT‐PCR, IHC and Western blotting. Results: In vitro and in vivo gain‐ and loss‐of‐function assays suggested that miR‐1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR‐1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR‐1258. In contrast, miR‐1258 inhibitor significantly reversed si‐GRB2‐induced GRB2 down‐regulation. Mechanistically, overexpression of miR‐1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway. Conclusions: Our results indicate that miR‐1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients. [ABSTRACT FROM AUTHOR]