Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.

UBXD family (UBXDF), a group of proteins containing ubiquitin regulatory X (UBX) domains, play a crucial role in the imbalance of proliferation and apoptotic in cancer. In this study, we summarised bioinformatics proof on multi-omics databases and literature on UBXDF's effects on cancer. Bioinformatics analysis revealed that Fas-associated factor 1 (FAF1) has the largest number of gene alterations in the UBXD family and has been linked to survival and cancer progression in many cancers. UBXDF may affect tumour microenvironment (TME) and drugtherapy and should be investigated in the future. We also summarised the experimental evidence of the mechanism of UBXDF in cancer, both in vitro and in vivo, as well as its application in clinical and targeted drugs. We compared bioinformatics and literature to provide a multi-omics insight into UBXDF in cancers, review proof and mechanism of UBXDF effects on cancers, and prospect future research directions in-depth. We hope that this paper will be helpful for direct cancer-related UBXDF studies.

Biomarker of Pulmonary Inflammatory Response in LUAD: miR-584-5p Targets RAB23 to Suppress Inflammation Induced by LPS in A549 Cells.

BACKGROUND: Pulmonary inflammatory response (PIR) is one of the prognostic risk factors of lung adenocarcinoma (LUAD), with a high mortality rate. OBJECTIVES: This study aims to investigate prognostic microRNA (miRNA) to improve clinical prognosis prediction and postoperative inflammation treatment in LUAD patients. METHODS: About 201 differentially expressed microRNAs (DE-miRNAs) in LUAD were mined by differential analysis. Univariate/multivariate Cox analyses established and validated prognostic risk miRNAs in TCGA-LUAD. KEGG and GO were used to link risk signatures and biological functions. After 48 hours of exposure to 50 ng/mL LPS, the miR-584-5p/RAB23 regulatory network was verified in qRT-PCR, Western Blotting, and the Luciferase Reporter Assay in A549 cells. RESULTS: MiR-584-5p and miR-101-3p were validated as riskscore correlated with LUAD patients' 1-year survival (p < 0.001) and participate in multiple inflammation-related pathways. RAB23, a RAS oncogene, is involved in inflammatory MAPK signaling. Evidence suggests that miR-584-5p regulates inflammation in LUAD by targeting RAB23. A549 cells were transfected with the mimic and inhibitor of miR-584-5p, confirming the negative regulatory relationship between miR-584-5p and RAB23. In the A549 induced by LPS, either over-expression of miR-584-5p or knock-down of RAB23 expression decreased the expression of inflammatory factors and increased cell viability. CONCLUSION: Prognostic-related risk miR-584-5p can regulate the expression of RAB23 at both the mRNA and protein levels, thereby influencing the development of a PIR in LUAD. This will have significant implications for the clinical prognosis prediction and therapy decision-making of LUAD patients with PIR.

Diagnostic implications of lncRNA NORAD in breast cancer.

This study aimed to assess the expression levels of non-coding RNA activated by DNA damage (NORAD) in the cells, tissues, and serum of breast cancer (BRCA) patients and benign breast nodules and investigate its association with clinicopathological characteristics and prognosis in BRCA. NORAD was analyzed using TCGA-BRCA, GSE77308, Cellminer, and Sangerbox databases, revealing its significance in BRCA prognosis, immune microenvironment, and cell function. Serum samples from 38 BRCA patients, 80 patients with benign breast nodules (50 fibroadenoma and 30 breast adenosis cases), and 42 healthy individuals were collected from Zhejiang Xiaoshan Hospital. NORAD expression was quantified using quantitative reverse transcription PCR (RT-qPCR). Differential NORAD expression between benign and malignant breast nodules and its relationship to clinicopathological characteristics were assessed. NORAD demonstrated elevated expression in BRCA patient serum compared to healthy individuals and those with benign breast nodules (P < 0.05). Moreover, its expression correlated with TNM-stage, lymph node metastasis, and luminal classification. These findings highlight the elevated NORAD expression in BRCA patient serum and its correlation with clinicopathological characteristics, providing insights into its potential as a diagnostic biomarker or therapeutic target.

The Emerging Roles of circRNAs in Papillary Thyroid Carcinoma: Molecular Mechanisms and Biomarker Potential.

Papillary thyroid carcinoma (PTC) is a common endocrine malignant tumor. The incidence of PTC has increased in the past decades and presents a younger trend. Accumulating evidence indicates that circular RNAs (circRNAs), featured with non-linear, closed-loop structures, play pivotal roles in tumorigenesis and regulate cell biological processes, such as proliferation, migration, and invasion, by acting as microRNA (miRNA) sponges. Additionally, due to their unique stability, circRNAs hold promising potential as diagnostic biomarkers and effective therapeutic targets for PTC treatment. In this review, we systematically arrange the expression level of circRNAs, related clinical characteristics, circRNA-miRNA-mRNA regulatory network, and molecular mechanisms. Furthermore, related signaling pathways and their potential ability of diagnostic biomarkers and therapeutic targets are discussed, which might provide a new strategy for PTC diagnosis, monitoring, and prognosis.

Machine learning modeling and prognostic value analysis of invasion-related genes in cutaneous melanoma.

In this study, we aimed to develop an invasion-related risk signature and prognostic model for personalized treatment and prognosis prediction in skin cutaneous melanoma (SKCM), as invasion plays a crucial role in this disease. We identified 124 differentially expressed invasion-associated genes (DE-IAGs) and selected 20 prognostic genes (TTYH3, NME1, ORC1, PLK1, MYO10, SPINT1, NUPR1, SERPINE2, HLA-DQB2, METTL7B, TIMP1, NOX4, DBI, ARL15, APOBEC3G, ARRB2, DRAM1, RNF213, C14orf28, and CPEB3) using Cox and LASSO regression to establish a risk score. Gene expression was validated through single-cell sequencing, protein expression, and transcriptome analysis. Negative correlations were discovered between risk score, immune score, and stromal score using ESTIMATE and CIBERSORT algorithms. High- and low-risk groups exhibited significant differences in immune cell infiltration and checkpoint molecule expression. The 20 prognostic genes effectively differentiated between SKCM and normal samples (AUCs >0.7). We identified 234 drugs targeting 6 genes from the DGIdb database. Our study provides potential biomarkers and a risk signature for personalized treatment and prognosis prediction in SKCM patients. We developed a nomogram and machine-learning prognostic model to predict 1-, 3-, and 5-year overall survival (OS) using risk signature and clinical factors. The best model, Extra Trees Classifier (AUC = 0.88), was derived from pycaret's comparison of 15 classifiers. The pipeline and app are accessible at https://github.com/EnyuY/IAGs-in-SKCM.

Regulation of LncRNAs and microRNAs in neuronal development and disease.

Non-coding RNAs (ncRNAs) are RNAs that do not encode proteins but play important roles in regulating cellular processes. Multiple studies over the past decade have demonstrated the role of microRNAs (miRNAs) in cancer, in which some miRNAs can act as biomarkers or provide therapy target. Accumulating evidence also points to the importance of long non-coding RNAs (lncRNAs) in regulating miRNA-mRNA networks. An increasing number of ncRNAs have been shown to be involved in the regulation of cellular processes, and dysregulation of ncRNAs often heralds disease. As the population ages, the incidence of neurodegenerative diseases is increasing, placing enormous pressure on global health systems. Given the excellent performance of ncRNAs in early cancer screening and treatment, here we attempted to aggregate and analyze the regulatory functions of ncRNAs in neuronal development and disease. In this review, we summarize current knowledge on ncRNA taxonomy, biogenesis, and function, and discuss current research progress on ncRNAs in relation to neuronal development, differentiation, and neurodegenerative diseases.

System biology approaches identified novel biomarkers and their signaling pathways involved in renal cell carcinoma with different human diseases.

Renal cell carcinoma (RCC) is a type of cancer that develops in the renal epithelium of the kidney. It is responsible for approximately 3% of adult malignancies, and 90-95% of neoplasms originate from the kidney. Advances in tumor diagnosis, innovative immune therapeutics, and checkpoint inhibitors-based treatment options improved the survival rate of patients with RCC accompanied by different risk factors. RCC patients with diabetes, hepatitis C virus (HCV), or obesity (OB) may have a comorbidity, and finding the risk factor for better clinical treatment is an urgent issue. Therefore, the study focused on network-based gene expression analysis approaches to learning the impact of RCC on other comorbidities associated with the disease. The study found critical genetic factors and signal transduction pathways that share pathophysiology and commonly use dysregulated genes of the illness. Initially, the study identified 385 up-regulated genes and 338 down-regulated genes involved with RCC. OB, chronic kidney disease (CKD), type 2 diabetes (T2D), and HCV significantly shared 28, 14, 5, and 3 genes, respectively. RCC shared one down-regulated gene versican (VCAN) with OB and HCV and one down-regulated gene oxidase homolog 2 (LOXL2) with OB and CKD. Interestingly, most of the shared pathways were linked with metabolism. The study also identified six prospective biomarkers, signaling pathways, and numerous critical regulatory and associated drug candidates for the disease. We believe that the discovery will help explain these diseases' complicated interplay and aid in developing novel therapeutic targets and drug candidates.

Long Non-coding RNA UCA1 Regulates SRPK1 Expression Through miR- 99b-3p in Ovarian Cancer.

BACKGROUND: Ovarian carcinoma (OC) is one of the most common malignancies of the female reproductive organs, with a low survival rate primarily due to the lack of effective methods for early diagnosis and prognosis. OBJECTIVE: In this article, our motivation is to explore the lncRNA-related network mechanisms involved in the pathogenesis of OC. METHODS: Public lncRNAs and mRNA expression datasets for OC were collected from the Gene Expression Omnibus (GEO) database. By integrated bioinformatics analysis, we constructed a UCA1-miRNA-mRNA network. We studied lncRNA-related molecular modulation mechanism in ovarian cancer cells based on MTT assay, dual luciferase reporter gene assays, quantitative realtime PCR, and western blotting. RESULTS: UCA1 was higher in ovarian tumor tissues and cells than normal tissues and cells. It was demonstrated in this study that knockdown of UCA1 inhibited ovarian cancer cell viability, which a miR-99b-3p inhibitor could reverse in vitro. Further, UCA1 was shown to regulate the expression of SRPK1 by directly binding to miR-99b-3p. CONCLUSION: These results suggest that UCA1 functions as an oncogene in ovarian cancer. Inhibition of UCA1/miR-99b-3p/SRPK1 axis may become a novel target for treating ovarian cancer.

The synergistic antitumor effect of IL-6 neutralization with NVP-BEZ235 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) still ranks among the top cancers worldwide with high incidence and mortality. Due to abnormal activation of the PI3K/AKT/mTOR signalling pathway in HCC, targeting this pathway represents a potential therapeutic strategy. NVP-BEZ235 is a novel dual-targeted ATP-competitive PI3K/mTOR inhibitor that has shown effective antitumor effects. In this study, we found that interleukin-6 (IL-6) was significantly increased after exposure to NVP-BEZ235, and we proposed a treatment in which an anti-IL-6 antibody was combined with NVP-BEZ235 for HCC. In vitro results revealed that targeted inhibition of IL-6 potentiated the antitumor effects of NVP-BEZ235 in HCC cells. The mechanism might be attributed to their synergistic inhibitory activity on the PI3K/AKT/mTOR signalling pathway. Furthermore, an in vivo study demonstrated that combined administration of NVP-BEZ235 and anti-IL-6 Ab reduced HCC tumour load more effectively than either NVP-BEZ235 or anti-IL-6 Ab treatment alone. These findings add guidance value to the analysis of HCC and provide a reference for clinical treatment.

Long Non-coding RNA ZFPM2-AS1: A Novel Biomarker in the Pathogenesis of Human Cancers.

Due to their biological activities in regulating dosage compensation, epigenetics, and cell differentiation, long non-coding RNAs (lncRNA) have been recognized as important regulators of the beginning and development of human malignancies. LncRNA dysregulation has a significant impact on a range of cellular functions, including proliferation, migration, invasion, and anti-apoptosis activity. Recently, aberrant expression of the long non-coding RNA zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) was observed in a range of solid tumors and correlated significantly with tumor size, histological differentiation, lymph node metastasis, malignant tumor (TNM) stage, short survival, and prognosis. Additional mechanical analysis indicated that ZFPM2-AS1 was involved in several cellular activities, including proliferation, migration, invasion, cell cycle progression, and apoptosis, through microRNAs (miRNAs), signaling pathways, and other biological components or proteins. This review summarizes the current status of research on ZFPM2-AS1 in various human malignancies and discusses its mechanism of action and clinical significance in tumor development and progression.

Advances in Pathophysiology of Triple-Negative Breast Cancer: The Potential of lncRNAs for Clinical Diagnosis, Treatment, and Prognostic Monitoring.

Recent studies have shown that long non-coding RNAs (lncRNAs) are involved in several gene expression regulation processes, including epigenetic regulation, transcriptional regulation, post-transcriptional regulation, and translation regulation. It also plays a crucial role in the regulation of several characteristics of cancer biology, and the dysregulation of lncRNA expression in cancer may be part of the cause of cancer progression. Meanwhile, more and more studies are trying to determine the association between lncRNA expression and TNBC, as well as the functional role and molecular mechanism of the abnormally expressed lncRNA. Therefore, this review lists some abnormal lncRNAs in TNBC, further analyzes their molecular mechanisms and biological roles in the development of TNBC, and summarizes the potential of lncRNAs as biomarkers and therapeutic targets of TNBC, so as to provide ideas for clinical diagnosis, targeted therapy, and prognosis monitoring of TNBC.

Clinicopathological implications of lncRNAs, immunotherapy and DNA methylation in lung squamous cell carcinoma: a narrative review.

OBJECTIVE: To explore the clinicopathological impact of lncRNAs, immunotherapy, and DNA methylation in lung squamous cell carcinoma (LUSC), emphasizing their exact roles in carcinogenesis and modes of action. BACKGROUND: LUSC is the second most prevalent form, accounting for around 30% of non-small cell lung cancer (NSCLC). To date, molecular-targeted treatments have significantly improved overall survival in lung adenocarcinoma patients but have had little effect on LUSC therapy. As a result, there is an urgent need to discover new treatments for LUSC that are based on existing genomic methods. METHODS: In this review, we summarized and analyzed recent research on the biological activities and processes of lncRNA, immunotherapy, and DNA methylation in the formation of LUSC. The relevant studies were retrieved using a thorough search of Pubmed, Web of Science, Science Direct, Google Scholar, and the university's online library, among other sources. CONCLUSIONS: LncRNAs are the primary components of the mammalian transcriptome and are emerging as master regulators of a number of cellular processes, including the cell cycle, differentiation, apoptosis, and growth, and are implicated in the pathogenesis of a variety of cancers, including LUSC. Understanding their role in LUSC in detail may help develop innovative treatment methods and tactics for LUSC. Meanwhile, immunotherapy has transformed the LUSC treatment and is now considered the new standard of care. To get a better knowledge of LUSC biology, it is critical to develop superior modeling systems. Preclinical models, particularly those that resemble human illness by preserving the tumor immune environment, are essential for studying cancer progression and evaluating novel treatment targets. DNA methylation, similarly, is a component of epigenetic alterations that regulate cellular function and contribute to cancer development. By methylating the promoter regions of tumor suppressor genes, abnormal DNA methylation silences their expression. DNA methylation indicators are critical in the early detection of lung cancer, predicting therapy efficacy, and tracking treatment resistance. As such, this review seeks to explore the clinicopathological impact of lncRNAs, immunotherapy, and DNA methylation in LUSC, emphasizing their exact roles in carcinogenesis and modes of action.

Roles of miRNA and lncRNA in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies, which makes its pathogenesis an important target for research. A growing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), plays a significant role in tumorigenesis. This review summarizes the roles of miRNA and lncRNA in the progression, diagnosis, and neoadjuvant chemotherapy of TNBC. Aberrantly expressed miRNA and lncRNA are listed according to their roles. Further, it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm, and more importantly, describes lncRNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level. Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment-they can be targeted in the future as a novel anticancer target of TNBC.

Bromo- and extraterminal domain protein inhibition improves immunotherapy efficacy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the majority of liver cancer and is the fourth most common cause of cancer-related death. Although advances in molecular targeted therapy have shown promise, none of these agents has yet demonstrated significant clinical benefit. Bromo- and extraterminal domain (BET) protein inhibitors have been considered potential therapeutic drugs for HCC but the biological activity remains unclear. This study found that BET protein inhibition did not effectively suppress the progression of HCC, using a transgenic HCC mouse model. Mechanistically, the BET protein inhibitor JQ1 upregulated the expression of programmed cell death-ligand 1 (PD-L1) on the plasma membrane in vivo and in vitro. Moreover, JQ1 enhanced the expression of Rab8A, which upregulated the expression of PD-L1 on the plasma membrane. This study also showed that JQ1 combined with anti-PD-L1 Ab effectively suppressed HCC progression, and this benefit was obtained by enhancing the activation and cytotoxic capabilities of CD8 T cells. These results revealed the crucial role and regulation of BET protein inhibition on the expression of PD-L1 in HCC. Thus, combining BET protein inhibition with immune checkpoint blockade offers an efficient therapeutic approach for HCC.

Current statuses of molecular targeted and immune checkpoint therapies in hepatocellular carcinoma.

Treatment of advanced hepatocellular carcinoma (HCC) still confronts great challenges due to high rate of therapeutic resistance. The emergence of systemic treatment with molecular targeted and immune checkpoint therapies has brought novel approaches towards patients with advanced HCC. However, sorafenib, as the first approved systemic treatment in 2007, only increased overall survival by three months in advanced HCC patients. Afterwards, little progress has been made for molecular targeted agents. Only four molecular drugs are empirically used in clinical practice. Lenvatinib acts as a first-line drug, whereas regorafenib, ramucirumab, and cabozantinib are defined as second-line drugs. Nevertheless, clinical findings reveal that overall survival remains unchanged. Albeit immunotherapy-based approaches are currently considered promising therapeutic strategies for advanced HCC, a minority of patients could benefit from them. These beneficiaries are to be accordingly identified. Combined immunotherapies with matched molecular targeted treatments would be a novel breakthrough. Herein, we summarize the current statuses of immunotherapies and molecular targeted drug therapies, and mainly identify clinically feasible chemoimmunotherapeutic strategies.

Suppression of YAP/TAZ-Notch1-NICD axis by bromodomain and extraterminal protein inhibition impairs liver regeneration.

Background and aims: Biological mechanisms that control liver regeneration remain poorly defined. However, these mechanisms are remarkable issues in the clinic that affect management of hepatic loss caused by liver surgery, traumatic injury, chronic infection, or liver poisoning. Increasing evidence has shown that various growth factors, cytokines, and metabolic signaling pathways affect the liver regenerative process. Our aim is to study the effect of bromodomain and extraterminal (BET) protein inhibition on liver regeneration and its mechanism. Methods: We studied the role of BET protein inhibitor, JQ1, in liver regeneration in a mouse model after 70% partial hepatectomy (PH). We evaluated yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) and Notch signaling pathways, which were affected by BET protein inhibitor in mouse hepatic tissues and primary hepatocytes in vivo and AML12 cell lines in vitro. We evaluated the relationship of YAP/TAZ and Notch signaling pathway using YAP/TAZ pathway inhibitor in liver regeneration in vivo. Moreover, we analyzed the relationship of YAP/TAZ and Notch signaling pathways via overexpression or RNA silencing of Yap in AML12 cells. Furthermore, we used Yap overexpression mouse model to examine whether it can rescue liver regeneration damage caused by inhibition of BET proteins. Results: In this study, we report that BET protein inhibitor JQ1 molecule impairs the early phase of liver regeneration in a mouse model after 70% PH. Mechanistically, YAP/TAZ and Notch1-NICD pathways were suppressed by BET protein inhibitor in mouse hepatic tissues and primary hepatocytes in vivo and mouse AML12 cell lines in vitro. By using YAP/TAZ pathway inhibitor, we confirmed that the liver regeneration and the activation of Notch pathway were impaired by the inhibition of YAP/TAZ pathway in vivo. Furthermore, the study showed that Yap knockdown by shRNA in normal mouse hepatic cell line downregulated Notch1 signal transduction, whereas Yap overexpression promoted Notch1-NICD signals. Specific overexpression of Yap in mouse liver could rescue the effect of BET protein inhibition on liver regeneration injury. Conclusion: These results revealed the crucial role of the YAP/TAZ-Notch1-NICD axis in liver regeneration. Therefore, BET protein inhibitors must be used in caution in the treatment of hepatic diseases by reason of its suppressive roles in liver regeneration.

Long non-coding RNA MALAT1 regulates BLCAP mRNA expression through binding to miR-339-5p and promotes poor prognosis in breast cancer.

The human genome transcribes a large amount of non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs. LncRNAs and microRNAs have been shown to play a critical regulatory role in tumorigenesis and progression. Competitive endogenous RNAs (ceRNAs) affect other RNAs transcription through competitively binding to common microRNAs (miRNAs). MALAT1 is a typical lncRNA that is markedly up-regulated in breast cancer. However, current understanding of the involvement of MALAT1 in breast cancer development and prognosis remains unclear. In the present study, the expression of MALAT1 in clinical samples of breast cancer tissues was found to be significantly up-regulated that was consistent with the result based on the dataset of the Cancer Genome Atlas (TCGA) at cBioportal. A negative correlation between overall survival and the expression of MALAT1 was statistically significant in the group of diagnosis age below 60 or in the group of infiltrating ductal carcinoma analyzed by TCGA database, which declared that MALAT1 might be a potentially useful prognostic factor. Furthermore, the combination of bioinformatics prediction with experimental verifications indicated that lncRNA MALAT1 can regulate BLCAP mRNA expression through binding to miR-339-5p.

Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer.

Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future.

Identification of an lncRNA­miRNA­mRNA interaction mechanism in breast cancer based on bioinformatic analysis.

Non­coding RNAs serve important roles in regulating the expression of certain genes and are involved in the principal biological processes of breast cancer. The majority of studies have focused on defining the regulatory functions of long non­coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs), and few studies have investigated how lncRNAs and miRNAs are transcriptionally regulated. In the present study, based on the breast invasive carcinoma dataset from The Cancer Genome Atlas at cBioPortal, and using a bioinformatics computational approach, an lncRNA­miRNA­mRNA network was constructed. The network consisted of 601 nodes and 706 edges, which represented the complex web of regulatory effects between lncRNAs, miRNAs and target genes. The results of the present study demonstrated that miR­510 was the most potent miRNA controller and regulator of numerous target genes. In addition, it was observed that the lncRNAs PVT1, CCAT1 and linc00861 exhibited possible interactions with clinical biomarkers, including receptor tyrosine­protein kinase erbB­2, estrogen receptor and progesterone receptor, demonstrated using RNA­protein interaction prediction software. The network of lncRNA­miRNA­mRNA interactions will facilitate further experimental studies and may be used to refine biomarker predictions for developing novel therapeutic approaches in breast cancer.

Let-7c-5p inhibits cell proliferation and induces cell apoptosis by targeting ERCC6 in breast cancer.

In this study, we found that let-7c-5p expression was clearly downregulated in breast cancer tissues compared with that of corresponding adjacent tissues. Furthermore, overexpression of let-7c-5p in MCF-7 breast cancer cells could significantly inhibit cell proliferation and induce cell apoptosis. The target genes of let-7c-5p were predicted by the way of bioinformatics, and validated by dual luciferase reporter assay and western blotting demonstrating that excision repair cross complementing 6 (ERCC6) gene was a direct target. Collectively, the present study suggested that let-7c-5p acted as a tumor suppressor in breast cancer possibly by negatively regulating ERCC6, which took an important part in nucleotide excision repair and it may provide a new potential strategy for breast cancer therapy.