lncRNAs In Breast Cancer Research Articles

Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions.

Breast cancer (BC) occupies the top spot among women on a global scale. The tumor has a significant degree of heterogeneity, displaying a notable prevalence of medication resistance, recurrence, and metastasis, rendering it one of the most lethal forms of malignant neoplasms. The timely identification, ongoing evaluation of therapeutic interventions, and accurate prediction of outcomes play crucial roles in determining the overall survival rates of women with BC. Nevertheless, the absence of precise biomarkers remains a significant determinant impacting the overall well-being and both the physical and emotional health of BC patients. Long noncoding RNA (lncRNA) exerts regulatory control over several genes and signaling pathways, hence assuming crucial roles in the development of neoplastic growth. Recently, research has indicated that the atypical expression of circulating lncRNAs in various biological bodily fluids has a noteworthy impact on the early detection, pathological categorization, staging, monitoring of therapy outcomes, and evaluation of prognosis in cases of BC. This article aims to assess the potential clinical utility of circulating lncRNAs in the context of BC focusing on specific primary signaling pathways; Wnt/β-catenin, Notch, TGF-β, and hedgehog (Hh), in addition to some therapeutic interventions.

Experimental and in silico analysis of LINC01279 expression in tumor of patients with breast cancer.

Breast cancer (BC) is characterized by the increase of malignant cells in the breast. The malignant cells begin in the lining of the breast milk glands or ducts (ductal epithelium). BC is the most frequent cancer in women, but it may also occur in males. Long non-coding RNAs (lncRNA) have been demonstrated to control the development and incidence of cancer. However, some lncRNAs experience potential changes in BC, but their role has not been well studied. LINC01279 is known as a valuable biomarker in gastric cancer but has not yet been studied in BC. Changes in LINC01279 expression levels in BC samples were investigated by microarray. Q-PCR was also used to evaluate the expression of LINC01279 in the tumor and normal adjacent samples of 30 BC patients. The LINC01279 co-expressed gene module was discovered using weighted gene correlation network analysis (WGCNA) on the relevant dataset. The top ten hub genes were determined using gene ontology (GO) functional enrichments on the co-expressed gene module. The results of the bioinformatics study showed an increase in LINC01279 expression levels (log2FC = 3.228749561, adj.P.Val = 1.69E - 12) in tumor samples compared to normal marginal tissue. Q-PCR results also showed a significant increase in LINC01279 expression (P-value = 0.0005) in tumor samples. WGCNA analysis identified that the black module is the LINC01279 co-expressed module, and functional annotation analysis of black module genes enriched in significant cancer-related pathways and processes, including cell growth and/or maintenance, regulation of immune response, regulation of cell proliferation, and epithelial-to-mesenchymal transition (EMT). Regarding the real-time PCR results, the analysis of expression patterns has illuminated a distinct association between the heightened expression levels of LINC01279, and the stages of cancer progression as well as the metastatic potential of tumors. However, intriguingly, our observations have failed to reveal any statistically significant correlations between the relative expression of LINC01279 and tumor grade classification, or the presence of ER, PR, and HER2 biomarkers. The present study could provide a new perspective on the molecular regulatory. Processes associated with BC pathogenic mechanisms are linked to the LINC01279, although further research is needed on the possible role of this lncRNA in BC.

Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis.

Breast cancer (BC) is the most prevalent cancer among women globally. Metastasis is the leading cause of mortality in most cancers. Early BC detection before metastasis can enhance survival rates. Understanding BC metastasis mechanisms could aid in developing metastasis-specific treatments. The role of long non-coding RNAs (lncRNA) in cancer progression is recognized, yet the importance of specific lncRNAs in BC, despite potential alterations, remains inadequately explored. We utilized bioinformatics tools to identify novel lncRNAs dysregulated in metastasis. To achieve this objective, the gene expression profile of GSE102484, encompassing metastatic and non-metastatic BC tissue samples, was analyzed using the limma package in R with cut-off criteria set at an adjusted p-value < 0.005 and |fold change (FC)| ≥ 0.5. We used WGCNA analysis to find co-expression genes for lncRNAs. Then, we identified hub genes and performed pathway enrichment to better understand the results. Considering the defined criteria, eight novels of dysregulated lncRNAs and top 10 miRNAs were identified. Dysregulated lncRNAs are found in yellow, green, brown, purple, and turquoise co-expression modules from WGCNA analysis. Enrichment analysis of these co-expressed modules revealed relevant pathways to metastasis, such as epithelial-to-mesenchymal transition and integrin cell-surface interactions, as well as regulation of HIF1-alpha. In addition, SDPR, TGFB1I1, ILF3, KIF4A, and COL5A1 were identified as hub genes. Based on DElncRNA-miRNADEmRNA connections and co-expression, we ultimately constructed lncRNA-associated ceRNA axes. The current study may identify novel lncRNAs implicated in BC metastasis; still, additional research is required to determine the potential functions of these lncRNAs in BC metastasis.

Effects of Differentially Methylated CpG Sites in Enhancer and Promoter Regions on the Chromatin Structures of Target LncRNAs in Breast Cancer.

Aberrant DNA methylation plays a crucial role in breast cancer progression by regulating gene expression. However, the regulatory pattern of DNA methylation in long noncoding RNAs (lncRNAs) for breast cancer remains unclear. In this study, we integrated gene expression, DNA methylation, and clinical data from breast cancer patients included in The Cancer Genome Atlas (TCGA) database. We examined DNA methylation distribution across various lncRNA categories, revealing distinct methylation characteristics. Through genome-wide correlation analysis, we identified the CpG sites located in lncRNAs and the distally associated CpG sites of lncRNAs. Functional genome enrichment analysis, conducted through the integration of ENCODE ChIP-seq data, revealed that differentially methylated CpG sites (DMCs) in lncRNAs were mostly located in promoter regions, while distally associated DMCs primarily acted on enhancer regions. By integrating Hi-C data, we found that DMCs in enhancer and promoter regions were closely associated with the changes in three-dimensional chromatin structures by affecting the formation of enhancer-promoter loops. Furthermore, through Cox regression analysis and three machine learning models, we identified 11 key methylation-driven lncRNAs (DIO3OS, ELOVL2-AS1, MIAT, LINC00536, C9orf163, AC105398.1, LINC02178, MILIP, HID1-AS1, KCNH1-IT1, and TMEM220-AS1) that were associated with the survival of breast cancer patients and constructed a prognostic risk scoring model, which demonstrated strong prognostic performance. These findings enhance our understanding of DNA methylation's role in lncRNA regulation in breast cancer and provide potential biomarkers for diagnosis.

Molecular Mechanism of lncRNAs in Regulation of Breast Cancer Metastasis; a Comprehensive Review.

Although the number of breast cancer deaths has decreased, and there have been developments in targeted therapies and combination treatments for the management of metastatic illness, metastatic breast cancer is still the second most common cause of cancer-related deaths in U.S. women. Numerous phases and a vast number of proteins and signaling molecules are involved in the invasion-metastasis cascade. The tumor cells penetrate and enter the blood or lymphatic vessels, and travel to distant organs via the lymphatic or blood vessels. Tumor cells enter cell cycle arrest, adhere to capillary beds in the target organ, and then disseminate throughout the organ's parenchyma, proliferating and enhancing angiogenesis. Each of these processes is regulated by changes in the expression of different genes, in which lncRNAs play a role in this regulation. Transcripts that are longer than 200 nucleotides and do not translate into proteins are called RNAs. LncRNA molecules, whose function depends on their unique molecular structure, play significant roles in controlling the expression of genes at various epigenetic levels, transcription, and so on. LncRNAs have essential functions in regulating the expression of genes linked to cell development in healthy and pathological processes, specialization, programmed cell death, cell division, invasion, DNA damage, and spread to other parts of the body. A number of cancer types have been shown to exhibit aberrant expression of lncRNAs. In this review, we describe the general characteristics, potential molecular mechanisms and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer.

A novel arginine methylation-associated lncRNA signature effectively predicts prognosis in breast cancer patients.

Breast cancer (BC) is a disease highly associated with epigenetic modification, and arginine methylation is particularly important in its genetic regulation. However, the role of arginine methylation related lncRNAs in breast cancer has not been studied. First, we identified the related lncRNAs (from TCGA database) according to the differentially expressed genes related to arginine methylation in breast cancer. Then the lncRNAs related to protein arginine methylation were obtained by regression analysis, and the risk score model was constructed. Finally, the cell experiment and subcutaneous tumor model verified that the arginine methylation related lncRNA z68871.1 in the model had a significant effect on the proliferation and invasion of breast cancer cells. In conclusion, we successfully constructed an arginine methylation related lncRNA model, which has strong predictive ability. At the same time, this study provides an experimental basis for exploring the mechanism of arginine methylation in BC and helps to find new biomarkers of BC.

Long Non-Coding RNAs (lncRNA) Are Key Factors in the Complex Puzzle of Breast Cancer Immunopathogenesis: A Review Study

Long non-coding RNAs (LnC RNAs) exert a substantial influence on breast cancer by exerting both positive and negative control over signaling pathways. LncRNAs are transcribed similarly to mRNA, however they do not undergo the process of translation to become proteins. Initially, these RNAs were classified as "Junk RNAs" since they were thought to lack any practical use. Comprehensive research has demonstrated that they play a vital role in the progression of various diseases, including malignancies, allergies, autoimmune and autoinflammatory disorders, infectious diseases, cardiovascular disease, and atherosclerosis. Despite multiple efforts, breast cancer continues to be a substantial concern and is one of the most prevalent forms of malignancy, especially among women. Recently, researchers have been dedicated to acquiring a deeper understanding of how complex signaling pathways are controlled by Lnc-RNAs in breast cancer. In the setting of breast cancer, Lnc-RNAs have a contradictory effect. The objective of this study is to Review and categorize previous studies An investigation was conducted to examine the impact of long non-coding RNAs on breast cancer. This will improve the capacity to identify topics of research that require further investigation in future studies.

Replenishment of TCA cycle intermediates and long-noncoding RNAs regulation in breast cancer

The tricarboxylic acid (TCA) cycle is an essential interface that coordinates cellular metabolism and is as a primary route determining the fate of a variety of fuel sources, including glucose, fatty acid and glutamate. The crosstalk of nutrients replenished TCA cycle regulates breast cancer (BC) progression by changing substrate levels-induced epigenetic alterations, especially the methylation, acetylation, succinylation and lactylation. Long non-coding RNAs (lncRNA) have dual roles in inhibiting or promoting energy reprogramming, and so altering the metabolic flux of fuel sources to the TCA cycle, which may regulate epigenetic modifications at the cellular level of BC. This narrative review discussed the central role of the TCA cycle in interconnecting numerous fuels and the induced epigenetic modifications, and the underlying regulatory mechanisms of lncRNAs in BC.

In silico identification and in vitro evaluation of MRPS30-DT lncRNA and MRPS30 gene expression in breast cancer.

It has been reported that long non-coding RNAs (lncRNAs) can play important roles in a variety of biological processes and cancer regulatory networks, including breast cancer. This study aimed to identify a novel upregulated lncRNA in breast cancer and its associated gene using bioinformatics analysis, and then evaluate their potential roles in breast cancer. Extensive in silico studies were performed using various bioinformatics databases and tools to identify a potential upregulated breast cancer-associated lncRNA and its co-expressed gene, and to predict their potential roles, functions, and interactions. The expression level of MRPS30-DT lncRNA and MRPS30 was assessed in both BC tissues and cell lines using qRT-PCR technology. MRPS30-DT lncRNA and MRPS30 were selected as target genes using bioinformatics analysis. We found that MRPS30-DT and MRPS30 were significantly overexpressed in BC tissues compared with normal tissues. Also, MRPS30 showed upregulation in all three BC cell lines compared with HDF. On the other hand, MRPS30-DT significantly increased in MDA-MB-231 compared with HDF. While the expression of MRPS30-DT was significantly dropped in the resistance cell line MCF/MX compared to HDF and MCF7. Moreover, bioinformatics analysis suggested that MRPS30-DT and MRPS30 may play a potential role in BC through their involvement in some cancer signaling pathways and processes, as well as through their interaction with TFs, genes, miRNAs, and proteins related to carcinogenesis. Overall, our findings showed the dysregulation of MRPS30-DT lncRNA and MRPS30 may provide clues for exploring new therapeutic targets or molecular biomarkers in BC.

LncRNA PRBC induces autophagy to promote breast cancer progression through modulating PABPC1-mediated mRNA stabilization.

Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer.

Expression analysis of PPAR-related lncRNAs in breast cancer

Breast cancer is a genetically heterogeneous disorder associated with dysregulation of several genes. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that is expressed by many tumoral cells such as transformed breast cancer cells. We investigated expressions of nine PPARγ-related lncRNAs, namely KCNIP2-AS1, TRHDE-AS1, FAM13A-AS1, ALDH1A1-AS2, SH3BP5-AS1, HID1-AS1, LINC01140, LIPE-AS1 and ABCA9-AS1 in paired breast cancer samples and non-tumoral tissues. Expression assays showed lower expression levels of TRHDE-AS1, ALDH1L1-AS2, KCNIP2-AS1, ABCA9-AS1, LIPE-AS1 and LINC01140 in tumoral compared with non-tumoral samples. The mentioned genes could differentiate between breast tumors and non-tumoral samples with AUC values ranging from 0.77 to 0.62 for LINC01140 and LIPE-AS1, respectively. The highest specificity and sensitivity values were reported for KCNIP2-AS1 and LINC01140, respectively. Significant correlations were reported between all pairs of genes in both tumoral and non-tumoral tissues. The most robust ones were between ABCA9-AS1 and KCNIP2-AS1 (correlation coefficient=0.85) in non-tumoral tissues and between LIPE-AS1 and TRHDE-AS1 (correlation coefficient=0.83) in tumoral tissues. There was a significant negative association between expression levels of KCNIP2-AS1 gene in tumor tissues and different histological grades. Besides, there was a significant negative association between expression levels of FAM13A-AS1, KCNIP2-AS1and LIPE-AS1 genes in tumor tissues and different mitotic rates. Taken together, PPARγ-related lncRNAs might be regarded as potential contributors to the pathogenesis of breast cancer.

Comprehensive analysis of ICD-related lncRNAs in predicting risk stratification, clinical prognosis and immune response for breast cancer.

Breast cancer (BRCA) represents a significant threat with high mortality rates due to relapse, metastasis, and chemotherapy resistance. As a regulated cell death process characterized by the induction of immunogenic signals, immunogenic cell death (ICD) has been identified as an effective anti-tumorigenesis approach. However, the comprehensive study and its clinical value of ICD-related lncRNAs in BRCA is still missing. The transcriptome matrix and corresponding clinical information of BRCA patients were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was performed to identify ICD-related lncRNAs (ICDRLs). To determine the prognostic value of the identified ICDRLs, univariate Cox regression analysis, LASSO algorithm, and multivariate Cox regression analysis were employed to construct a risk model. The prognostic risk model was subsequently evaluated using univariate and multivariate Cox regression analysis, as well as Nomogram analysis. In vitro experiments were also conducted to validate the bioinformatics findings using quantitative real-time PCR (qRT-PCR). We established a prognostic risk signature consisting of five ICDRLs. The prognostic value of this model was subsequently confirmed in guiding BRCA prognostic stratification. Furthermore, we explored the correlation of the risk score with various clinical characteristics and chemotherapy response. qRT-PCR result confirmed the abnormal expression of ICDRLs, which was consistent with the bioinformatics data. Our findings provide evidence of the critical role of ICDRLs in BRCA and offer a novel perspective for exploring precise treatment options for BRCA patients.

Lnc‑RGS5 sponges miR‑542‑5p to promote FoxM1/VEGFA signaling and breast cancer cell proliferation.

Breast cancer (BRCA) exhibits a high incidence rate among women worldwide. LOC127814295 (ENSG00000232995), termed long non‑coding (lnc)‑regulator of G protein signaling 5 (RGS5), is a novel lncRNA with a genomic region overlapping with protein‑coding gene RGS5. Results obtained using The Cancer Genome Atlas demonstrated that lnc‑RGS5 was deregulated in diverse cancer types, including BRCA; however, the functional role of lnc‑RGS5 remains unclear. Results of the present study demonstrated that lnc‑RGS5 was upregulated in BRCA tissues compared with healthy samples (n=30; P<0.0001), and was associated with the overall survival of patients with triple‑negative BRCA (n=106; P<0.05). Moreover, lnc‑RGS5 expression was significantly higher in triple‑negative BRCA samples than in LumA, LumB, or Her2 subtypes (P<0.05). Functionally, lnc‑RGS5 upregulation promoted BRCA cell proliferation invitro, whereas lnc‑RGS5 knockdown elicited the opposite function. Stable knockdown of lnc‑RGS5 inhibited tumor cell proliferation invivo. Bioinformatics analysis revealed that lnc‑RGS5 was significantly associated with RNA binding involved in post‑transcriptional gene silencing (P=0.002). Mechanistically, lnc‑RGS5 functions as a competing endogenous RNA via competitively sponging miR‑542‑5p to upregulate forkhead box M1 (FoxM1) and the VEGFA/Neuropilin 1 axis; thus, promoting BRCA cell proliferation invitro. Moreover, rescue experiments validated that the lnc‑RGS5/miR‑542‑5p/FoxM1 axis promoted BRCA cell growth invivo. Collectively, results of the present study demonstrated that lnc‑RGS5 may exhibit potential as a novel oncogenic lncRNA in BRCA. The present study may provide a novel theoretical basis for the role of lncRNA in the targeted therapy of BRCA.

An angiogenesis-related lncRNA signature predicts the immune microenvironment and prognosis of breast cancer.

Both angiogenesis and lncRNAs play crucial roles in the development and progression of breast cancer. Considering the unknown association of angiogenesis and lncRNAs in breast cancer, we aim to identify angiogenesis-related lncRNAs (ARLs) and explore their prognostic value. Here, based on analysis of The Cancer Genome Atlas database, the correlation between ARL and the prognosis and immune infiltration landscape of breast cancer were investigated. Eight ARLs (MAFG-DT, AC097478.1, AL357054.4, AL118556.1, SNHG10, MED14OS, OTUD6B-AS1, and CYTOR) were selected to construct the risk model as a prognostic signature. The survival rate of the patients in the high-risk group was lower than that in the low-risk group. The ARL signature was an independent prognostic predictor, and areas under the curve of 1-, 3-, and 5-year survival were 0.745, 0.695, and 0.699, respectively. The prognostic ARLs were associated with the immune infiltration landscape and could indicate the immune status, immune response, tumor mutational burden, and drug sensitivity of patients with breast cancer. Furthermore, qRT-PCR of clinical samples revealed that OTUD6B-AS1 was correlated with prognostic pathological parameters. OTUD6B-AS1 promoted breast cancer cell proliferation, wound healing, migration, invasion, and human umbilical vein endothelial cells tube formation. Mechanistically, OTUD6B-AS1 regulated EMT- and angiogenesis-related molecules. Taken together, we constructed and verified a robust signature of eight ARLs for the prediction of survival in patients with breast cancer, and the characterization of the immune infiltration landscape. Our findings suggest that OTUD6B-AS1 could be a therapeutic target for patients with breast cancer.

Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway.

Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

Exploration of epithelial-mesenchymal transition-related lncRNA signature and drug sensitivity in breast cancer.

Breast cancer (BRCA) has become the most diagnosed cancer worldwide for female and seriously endanger female health. The epithelial-mesenchymal transition (EMT) process is associated with metastasis and drug resistance in BRCA patients. However, the prognostic value of EMT-related lncRNA in BRCA still needs to be revealed. The aim of this study is to construct an EMT-related lncRNA (ERL) signature with accuracy predictive ability for the prognosis of BRCA patients. RNA-seq expression data and Clinical characteristics obtained from the TCGA (The Cancer Genome Atlas) were used in the study. First, we identified the EMT-related lncRNA by the Pearson correlation analysis. An EMT-related lncRNAs prognostic risk signature was constructed using univariate Cox regression and Lasso-penalized Cox regression analyses. The model's performance was validated using Kaplan-Meier (KM) survival analysis, ROC curve and C-index. Finally, a nomogram was constructed for clinical practice in evaluating the patients with BRCA and validated by calibration curve and decision curve analysis (DCA). We also evaluated the drug sensitivity of signature lncRNA and the tumor immune cell infiltration in breast cancer. We constructed a 10-lncRNA risk score signature based on the lncRNAs associated with the EMT process. We could assign BRCA patients to the high- and low-risk group according to the median risk score. The prognostic risk signature showed excellent accuracy and demonstrated sufficient independence from other clinical characteristics. The immune cell infiltration analysis showed that the prognostic risk signature was related to the infiltration of the immune cell subtype. Drug sensitivity analysis proved ERLs signature could effectively predict the sensitivity of patients to common chemotherapy drugs in BRCA and provide guidance for chemotherapy drugs for high-risk and low-risk patients. Our ERL signature and nomogram have excellent prognostic value and could become reliable tools for clinical guidance.

Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer.

Background: Cuproptosis-related lncRNAs regulate the biological functions of various cancers. However, the role of cuproptosis-related lncRNAs in breast cancer remains unclear. In this study, we investigated the biological functions and clinical applications of cuproptosis-related lncRNAs in breast cancer. Methods: The Cancer Genome Atlas (TCGA) database and the GSE20685 dataset were used for screening cuproptosis-related lncRNAs. Colony formation and CCK-8 kit assays were performed for detecting the proliferative function of cuproptosis-related lncRNAs, whereas wound healing, migration, and invasion assays were performed for detecting the metastatic regulation of cuproptosis-related lncRNAs in breast cancer. Finally, a prognostic cuproptosis-related lncRNA model was constructed using LASSO Cox regression analysis for detecting survival and sensitivity to conventional treatment (endocrine therapy, chemotherapy, and radiotherapy) and novel therapy (PARP and CDK4/6 inhibitors). Results: In this study, we screened six cuproptosis-related lncRNAs associated with the survival of patients with breast cancer. Biofunctional experiments indicated that cuproptosis-related lncRNAs play essential roles in regulating the proliferation and metastasis of breast cancer cells. Finally, we applied a model of six cuproptosis-related lncRNAs to classify the patients into high- and low-risk groups. High-risk group patients exhibited worse survival rates (p < 0.001) and lower sensitivity to chemotherapy, endocrine therapy, and radiation therapy. Compared with high-risk patients, low-risk patients exhibited a lower expression of CDK4/6 inhibitor-resistant biomarkers (CCNE1, E2F1, and E2F2) and PARP inhibitor-resistant biomarkers (BRCA1/BRCA2), indicating that patients in the low-risk group were more suitable for PARP inhibitor and CDK4/6 inhibitor application. Conclusion: Cuproptosis-related lncRNAs are essential for regulating the biological functions of breast cancer, and they have the potential to predict prognosis and sensitivity of breast cancer to various therapies.

LncSNHG3 drives breast cancer progression by epigenetically increasing CSNK2A1 expression level.

Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles in the initiation and progression of cancer. Here, we report that small nucleolar RNA host gene 3 (SNHG3) is a key regulator of breast cancer progression. We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in breast cancer. The effects of SNHG3 on breast cancer were investigated via in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and Western blot). The mechanism of SNHG3 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay. We found that SNHG3 expression was upregulated in breast cancer tissues and that its high expression level was associated with poor survival. We also found that high SNHG3 expression was partly induced by STAT3. Moreover, SNHG3 knockdown significantly repressed breast cancer cell growth both in vitro and in vivo. In the cytoplasm, SNHG3 facilitated the expression of Casein kinase II-A1 (CSNK2A1) by absorbing miR-485-5p and recruiting the HuR protein, participating in the malignant progression of breast cancer. Taken together, our study reveals a SNHG3-based regulatory network, which plays an oncogenic role in breast cancer and suggests that SNHG3 may serve as a potential target for the diagnosis and treatment of breast cancer.

Long Non-Coding RNAs, Cell Cycle, and Human Breast Cancer.

The long non-coding RNAs (lncRNAs) constitute an important class of the human transcriptome. The discovery of lncRNAs provided one of many unexpected results of the post-genomic era and uncovered a huge number of previously ignored transcriptional events. In recent years, lncRNAs are known to be linked with human diseases, with particular focus on cancer. Growing evidence has indicated that dysregulation of lncRNAs in breast cancer (BC) is strongly associated with the occurrence, development, and progress. Increasing numbers of lncRNAs have been found to interact with cell cycle progression and tumorigenesis in BC. The lncRNAs can exert their effect as a tumor suppressor or oncogene and regulate tumor development through direct or indirect regulation of cancer-related modulators and signaling pathways. What is more, lncRNAs are excellent candidates for promising therapeutic targets in BC due to the features of high tissue and cell-type specific expression. However, the underlying mechanisms of lncRNAs in BC still remain largely undefined. Here, we concisely summarize and sort out the current understanding of research progress in relationships of the roles for lncRNA in regulating the cell cycle. We also summarize the evidence for aberrant lncRNA expression in BC, and the potential for lncRNA to improve BC therapy is also discussed. Together, lncRNAs can be considered as exciting therapeutic candidates whose expression can be altered to impede BC progression.

BCLncRDB: a comprehensive database of LncRNAs associated with breast cancer.

Breast cancer, the most common cancer in women, is characterized by high morbidity and mortality worldwide. Recent evidence has shown that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of breast cancer. However, despite increasing data and evidence indicating the implication of lncRNAs in breast cancer, no web resource or database exists primarily for lncRNAs associated with only breast cancer. Therefore, we developed a manually curated, comprehensive database, "BCLncRDB," for lncRNAs associated with breast cancer. For this, we collected, processed, and analyzed available data on breast cancer-associated lncRNAs from different sources, including previously published research articles, the Gene Expression Omnibus (GEO) Database of the National Centre for Biotechnology Information (NCBI), The Cancer Genome Atlas (TCGA), and the Ensembl database; subsequently, these data were hosted at BCLncRDB for public access. Currently, the database contains 5324 unique breast cancer-lncRNA associations and has the following features: (i) a user-friendly, easy-to-use web interface for searching and browsing about lncRNAs of the user's interest, (ii) differentially expressed and methylated lncRNAs, (iii) stage- and subtype-specific lncRNAs, and (iv) drugs, subcellular localization, sequence, and chromosome information of these lncRNAs. Thus, the BCLncRDB provides a one-stop dedicated platform for exploring breast cancer-related lncRNAs to advance and support the ongoing research on this disease. The BCLncRDB is publicly available for use at http://sls.uohyd.ac.in/new/bclncrdb_v1 .