Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer.

BACKGROUND: Breast cancer (BC) remains a public health problem. Tamoxifen (TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear. AIM: To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients. METHODS: High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1. RESULTS: EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance. CONCLUSION: This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

Body Mass Index at Diagnosis as a Prognostic Factor for Early-Stage Invasive Breast Cancer after Surgical Resection.

BACKGROUND: The aim of this study was to investigate the association between body mass index (BMI) and prognosis of Chinese women with breast cancer. PATIENTS AND METHODS: 3,380 primary breast cancer patients who underwent surgery from 2010 to 2012 were selected and classified as low BMI group (BMI < 25.0) and high BMI group (BMI ≥ 25.0). The follow-up data for disease-free survival (DFS) and overall survival (OS) were obtained from 3,178 patients (median follow-up of 58 months). Cox regression analysis was used to evaluate the effect of BMI on DFS and OS. RESULTS: The high BMI group showed more aggressive pathological features. BMI was negatively associated with OS (hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.06-1.66; p = 0.012) but not DFS (HR 1.15, 95% CI 0.94-1.40; p = 0.17). Furthermore, when stratified by age, BMI was significantly and negatively associated with OS (HR 1.43, 95% CI 1.05-1.95; p = 0.025) in patients above 50 years of age, but this effect was not detected in younger patients. CONCLUSION: BMI was an independent prognostic factor of OS in Chinese women with breast cancer, and age might be a mitigating factor. Among patients above 50 years of age, those with a high BMI were at greater risk of poor prognosis compared to individuals with a low BMI.

The expression and biological function of the PHF2 gene in breast cancer.

PHD Finger Protein 2 (PHF2), as a protein code and a transcription regulatory gene, is a member of the Jumonji-C domain (JmjC). PHF2 is located at human chromosome 9q22.31 and is frequently decreased in various malignancies. However, the definite role of PHF2 in breast cancer remains unclear. To detect the expression and function of PHF2 in breast cancer, a q-PCR assay was used to detect the mRNA expression of PHF2 in breast cancer cell lines and paired breast cancer tissues, and immunohistochemistry was used to test the protein expression in breast cancer tissues and adjacent tissues. In addition, an adenovirus vector system was utilized to upregulate the expression of PHF2 in breast cancer cells. In our study, we found that PHF2 was down-expressed in breast cancer on both the mRNA and protein levels and the low expression of PHF2 was significantly associated with lymph node metastasis, Ki67 positive rate, ER negative expression and poor prognosis in breast cancer patients. The ectopic expression of PHF2 obviously inhibited the proliferation of breast cancer cell lines and the growth of xenograft tumors. Due to the tumor suppressor signature of PHF2 in breast cancer, we have reasons to believe that it could be a promoting marker and target for the prognosis and therapy of breast cancer.