Analysis of lncRNA-related studies of ivermectin-sensitive and -resistant strains of Haemonchus contortus.

In this study, 858 novel long non-coding RNAs (lncRNAs) were predicted as sensitive and resistant strains of Haemonchus contortus to ivermectin. These lncRNAs underwent bioinformatic analysis. In total, 205 lncRNAs significantly differed using log2 (difference multiplicity) > 1 or log2 (difference multiplicity) < - 1 and FDR < 0.05 as the threshold for significant difference analysis. We selected five lncRNAs based on significant differences in expression, cis-regulation, and their association with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. These expressions of lncRNAs, namely MSTRG.12610.1, MSTRG.8169.1, MSTRG.6355.1, MSTRG.980.1, and MSTRG.9045.1, were significantly downregulated. These findings were consistent with the results of transcriptomic sequencing. We further investigated the relative expression of target gene mRNAs and the regulation of mRNA and miRNA, starting with lncRNA cis-regulation of mRNA, and constructed a lncRNA-mRNA-miRNA network regulation. After a series of statistical analyses, we finally screened out UGT8, Unc-116, Fer-related kinase-1, GGPP synthase 1, and sart3, which may be involved in developing drug resistance under the regulation of their corresponding lncRNAs. The findings of this study provide a novel direction for future studies on drug resistance targets.

Exploring the therapeutic potential of ADC combination for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Currently, standard treatment options for TNBC are limited to surgery, adjuvant chemotherapy, and radiotherapy. However, these treatment methods are associated with a higher risk of intrinsic or acquired recurrence. Antibody-drug conjugates (ADCs) have emerged as a useful and promising class of cancer therapeutics. ADCs, also known as "biochemical missiles", use a monoclonal antibody (mAb) to target tumor antigens and deliver a cytotoxic drug payload. Currently, several ADCs clinical studies are underway worldwide, including sacituzumab govitecan (SG), which was recently approved by the FDA for the treatment of TNBC. However, due to the fact that only a small portion of TNBC patients respond to ADC therapy and often develop resistance, growing evidence supports the use of ADCs in combination with other treatment strategies to treat TNBC. In this review, we described the current utilization of ADCs and discussed the prospects of ADC combination therapy for TNBC.

Suicide rates among people with serious mental illness: a systematic review and meta-analysis.

BACKGROUND: People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia). METHODS: PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex. RESULTS: Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3-406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5-417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4-1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60-2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7-50.4)]. CONCLUSIONS: The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

Detection of Brucella S2 vaccine strain by a loop-mediated isothermal amplification (LAMP) method.

Introduction: Brucellosis is a highly prevalent zoonotic disease caused by Brucella spp. Brucella suis S2 vaccination is an effective strategy to prevent animal brucellosis. However, S2 induces antibodies against the smooth lipopolysaccharide,making it challenging to distinguish field infected from vaccinated livestock. Early and accurate diagnosis is essential for infection control and prevention. In this study, we aimed to develop a quick and accurate assay to distinguish the BrucellaS2 vaccine strain from closely related B. abortus and B. melitensis. Methods: Whole-genome sequencing of B. suis S2 was performed, and the sequence was compared with that of the genomes of B. abortus and B. melitensis. One specific gene, GL_0002189, was selected as a marker to differentiate the BrucellaS2vaccine strain from B. abortus and B. melitensis. A loop-mediated isothermal amplification (LAMP) assay was developed, based on the GL_0002189 gene, and then assessed for target specificity, lower limit of detection, and repeatability. Results: Our results revealed that there was no cross-reaction with other strains, and the LAMP assay displayed high sensitivity for detecting S2 with a minimum detection limit of 18.9×103 copies/µL DNA input, it is nearly 100 times higher than conventional PCR technology. Concordance between the LAMP assay and a conventional polymerase chain reaction method was assessed using 54 blood samples collected from sheep with suspected brucellosis. Total concordance between the two assays was 92.6%, without a significant difference (p > 0.05) in the test results. Conclusion: This is the first report of a LAMP assay for the detection of the B. suis S2vaccine strain. Our approach can be helpful for the control and eradication of brucellosis, and its simplicity in requiring no specialized equipment or personnel makes it useful for implementation in resource-limited settings as well as for field use.

The Effect of Health Literacy Intervention on Patients with Diabetes: A Systematic Review and Meta-Analysis.

Relevant studies published between January 2010 and June 2021 were identified through relevant databases, including the Science Citation Index Expanded (SCIE) database of Web of Science, PubMed, and Embase, in order to assess the effect of health literacy (HL) intervention on patients with diabetes. A total of 21 articles were eligible. The results showed that: (1) this review involved different HL assessment tools, most of which were self-designed scales and assessment tools focused on measuring functional HL. (2) The differences in glycosylated hemoglobin (HbA1c) (weighted mean difference [WMD] = -0.78, 95% confidence interval [CI]: -0.94, -0.62) and medication adherence (standardized mean difference [SMD] = 1.85, 95% CI: 0.19, 3.52) between the HL intervention group and the usual care group were statistically significant. There was no significant improvement in systolic blood pressure (SMD = -0.05, 95% CI: -0.34, 0.25). Furthermore, this review reported that self-efficacy (SMD = 0.85, 95% CI: 0.65, 1.04) was increased, and the level of HL was improved. In the assessments of risk of bias, 90% of the studies were classified as medium. The quality of the evidence of medication adherence was very low, and the reliability of the conclusions was not enough to confirm the effect of HL.

Comprehensive Analysis of the Expression and Prognosis for RAD51 Family in Human Breast Cancer.

Purpose: The RAD51 family of genes, including RAD51 and the five RAD51-like paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3), are known to be crucially associated with DNA damage repair pathway. Increasing evidence indicated that RAD51 family members were implicated in breast cancer tumorigenesis. However, their biological roles and prognostic values in breast cancer have yet to be clarified. Methods: In this study, by using the Oncomine and GEPIA databases, we explored the transcriptional levels of RAD51 family members in breast cancer. Besides, the associations between RAD51 family expression and clinical features were evaluated by using the UALCAN database and Kaplan-Meier (KM) Plotter. We also analyzed the mutations of the RAD51 family and differentially altered genes from the cBioPortal database. Results: We found that RAD51 mRNA was significantly elevated in breast cancer samples than in normal tissues, while XRCC2 mRNA was downregulated. Besides, a remarkable correlation was detected between the expression of RAD51/RAD51B/XRCC2 genes and the breast cancer stage. Survival analysis utilizing the KM Plotter indicated that high RAD51 and XRCC3 mRNA was associated with a poor prognosis. Conversely, RFS data suggested that high levels of RAD51B/RAD51C/RAD51D/XRCC2 were associated with a favorable prognosis. Moreover, a high genetic variation rate of RAD51C (7%) was detected in breast cancer patients. Conclusion: Conclusively, we implied that RAD51 and XRCC3 might be potential targets for precision therapy in breast cancer and the RAD51B/RAD51C/RAD51D/XRCC2 genes have significant values for breast cancer prognosis.

COVID-19 in patients with systemic lupus erythematosus: A systematic review.

The objectives of the study were to review the articles to identify (a) the epidemiology of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19); (b) the clinical characteristics of SLE patients with COVID-19; (c) the treatment of COVID-19 in SLE patients; and (d) the impact of COVID-19 pandemic on SLE patients. PubMed was systematically reviewed for literature published from December 2019 to June 2021. Our search was limited to human studies, with language restriction of English. Studies were included if they reported COVID-19 in SLE patients. Our systematic review included 52 studies. The prevalence of COVID-19 infection ranged from 0.0% to 18.1% in SLE patients, and the hospitalisation rates ranged from 0.24% to 10.6%. COVID-19 infection is likely to mimic SLE flare. Hydroxychloroquine (HCQ) was ineffective in prevention of COVID-19, and SLE patients with COVID-19 faced difficulty in healthcare access, had financial constraints and suffered from psychological distress during the pandemic. The pandemic had a significant effect on mental and physical health. Adequate healthcare access, along with containment policies, social distancing measures and psychological nursing was required.

Transcriptome profiling provides insights into the molecular mechanisms of maize kernel and silk development.

BACKGROUND: Maize kernel filling, which is closely related to the process of double fertilization and is sensitive to a variety of environmental conditions, is an important component of maize yield determination. Silk is an important tissue of maize ears that can discriminate pollen and conduct pollination. Therefore, investigating the molecular mechanisms of kernel development and silk senescence will provide important information for improving the pollination rate to obtain high maize yields. RESULTS: In this study, transcript profiles were determined in an elite maize inbred line (KA105) to investigate the molecular mechanisms functioning in self-pollinated and unpollinated maize kernels and silks. A total of 5285 and 3225 differentially expressed transcripts (DETs) were identified between self-pollinated and unpollinated maize in a kernel group and a silk group, respectively. We found that a large number of genes involved in key steps in the biosynthesis of endosperm storage compounds were upregulated after pollination in kernels, and that abnormal development and senescence appeared in unpollinated kernels (KUP). We also identified several genes with functions in the maintenance of silk structure that were highly expressed in silk. Further investigation suggested that the expression of autophagy-related genes and senescence-related genes is prevalent in maize kernels and silks. In addition, pollination significantly altered the expression levels of senescence-related and autophagy-related genes in maize kernels and silks. Notably, we identified some specific genes and transcription factors (TFs) that are highly expressed in single tissues. CONCLUSIONS: Our results provide novel insights into the potential regulatory mechanisms of self-pollinated and unpollinated maize kernels and silks.

The complete mitochondrial genome of Syritta pipiens (Linnaeus, 1758) (Diptera: Syrphidae) and phylogenetic analysis.

The complete mitochondrial genome (mitogenome) of Syritta pipiens (Linnaeus, 1758) was sequenced with 15,745 bp in length including 37 genes and a non-coding region. The overall nucleotide composition showed a strong AT bias. Most protein-coding genes (PCGs) used ATN as the start codon while ATP6 and ND1 used TTG, and stopped by TAA or TAG but ND5 ended with an incomplete T. Phylogenetic trees were reconstructed based on the 24 complete mitochondrial sequences from Syrphidae using the methods of maximum-likelihood (ML) and Bayesian inference (BI), resulted in S. pipiens clustered into the clade of Eristalinae, which conformed to the traditional classification, but the trees did not support the monophyly of Eristalinae. More molecular data is needed for further study.

Incidence of suicide mortality among childhood cancer survivors: A population-based retrospective study.

The aim of our study was to investigate the suicide rates among childhood cancer survivors and assess factors associated with higher suicide risk. A review of data from Surveillance, Epidemiology, and End Results (SEER) program from 1975 to 2016 was performed for this study. This program is based on the US population and is supported by the US National Cancer Institute (NCI). Survivors diagnosed with childhood cancer were recorded. There were 40 suicides among 567,233 person-years, giving a suicide rate of 7.1 per 100,000 person-years. Compared with cancer diagnosed between 10 and 14 years old, survivors with cancer diagnosed between 0 and 4 years old had lower suicide risk. Females had a lower risk of suicide than males. Compared with survivors of thyroid cancer, the aHRs were 0.16 for acute lymphocytic leukemia, 0.15 for nodal Hodgkin's lymphoma, 0.14 for brain cancers and 0.09 for kidney cancers. Most suicides occurred after 15 years old. Suicide was a problem for survivors, especially those with thyroid cancer. Beside treating patients holistically, early psychological interventions such as communicating effectively, providing social support and follow-up care related to psychological health are needed.

Caregiver Burden Among Primary Family Caregivers of Patients Undergoing Hematopoietic Stem Cell Transplantation: A Cross-sectional Study From Suzhou, China.

BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) require extensive care, and their caregivers were previously found to experience high levels of caregiver's burden. However, the current status of HSCT patient caregiver burden in Suzhou, China, is still unknown. OBJECTIVE: To investigate the current status of caregiver burden among family caregivers of HSCT patients from Suzhou, China, and explore the related factors of caregiver burden. METHODS: This cross-sectional study enrolled 116 HSCT patient-caregiver dyads. The following measurement tools were used: a demographic questionnaire, Zarit Burden Interview, and World Health Organization Quality of Life questionnaire (brief version). Multiple regression model was used to analyze the factors associated with caregiver burden, and the relationship between caregiver burden and quality of life was analyzed. RESULTS: Caregivers' marital status, family monthly income, duration of caregiving, daily caregiving time, other cocaregivers, transplant-related complications, and relapse were closely related to caregiver burden, and 75.4% of the variance in caregivers' burden was explained by these factors. A negative correlation between caregiver burden and quality of life was noted. CONCLUSION: The HSCT patient caregivers' burden noted in this study was higher than that found in previous studies. The quality of life of HSCT patient caregivers is lower than that of the average Chinese population and decreases with a greater sense of burden. IMPLICATIONS FOR PRACTICE: Hematopoietic stem cell transplantation patient caregivers should be given appropriate social support to reduce their burden of care. Factors identified in this study may help center future intervention programs on caregivers who need help the most.

c-myc regulates the sensitivity of breast cancer cells to palbociclib via c-myc/miR-29b-3p/CDK6 axis.

Palbociclib, a CDK4/6 inhibitor, has been granted accelerated approval by US FDA for hormone receptor-positive HER2-negative metastatic breast cancer. To determine potential biomarkers of palbociclib sensitivity to assist in patient selection and clinical development, we investigated the effects of palbociclib in a panel of molecularly characterized breast cancer cell lines. We quantified palbociclib sensitivity and c-myc expression in 11 breast cancer cell lines, 124 breast cancer samples, and The Cancer Genome Atlas database. We found non-TNBC subtypes were more sensitive to palbociclib than TNBC. Activation of c-myc led to differential palbociclib sensitivities, and further inhibition of c-myc enhanced palbociclib sensitivity. Moreover, we identified for the first time a c-myc/miR-29b-3p/CDK6 axis in breast cancer that could be responsible for c-myc-induced palbociclib insensitivity, in which c-myc activation resulted in downregulation of miR-29b-3p, further activated CDK6 and inhibited cell-cycle arrest at G1 phase. Moreover, downregulated (inactived) c-myc-induced oncogenic addiction could increase palbociclib efficacy, using both Xenograft model and patient-derived tumor xenograft (PDTX) model. Our finding extends the concept of combined blockade of the CDK4/6 and c-myc signaling pathways to increase palbociclib sensitivity, making c-myc a promising biomarker for palbociclib sensitivity in breast cancer.

Factors Contributing to Drug Release From Enteric-Coated Omeprazole Capsules: An In Vitro and In Vivo Pharmacokinetic Study and IVIVC Evaluation in Beagle Dogs.

This study was performed to explore factors influencing the release of the proton pump inhibitor omeprazole from enteric-coated capsules in vitro and absorption in vivo in beagle dogs. Enteric-coated pellets with different enteric coating materials and coating levels were designed and prepared. All self-prepared formulations were characterized in vitro as well as in vivo and compared to the brand and generic commercial products. Evaluation of the corresponding release profiles suggested that coating material was the most critical factor. Enteric coating level determined the lag time before initiation of drug release, and subcoating level affected the drug release rate. Pharmacokinetic studies were performed in beagle dogs to further confirm the influence of formulation factors on drug absorption. Medium at pH 6.8 was a more biorelevant condition for in vitro drug release tests, although medium at pH 6.0 was better for discriminating release profiles of different formulations. A multiple level C in vitro/in vivo correlation was preliminarily established by which Tmax and Cmax of omeprazole formulations could be predicted with release parameters such as Tlag and T25. These results may facilitate quality evaluation and potentially improve the clinical efficacy of generic omeprazole products.

PIK3CA mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis.

Background: There is conflicting evidence regarding the association between PIK3CA mutations and clinicopathological features of colorectal cancer (CRC). We performed a comprehensive meta-analysis investigating the association between PIK3CA mutations and clinicopathological features in CRC, including subgroup analysis of mutations in exons 9 and 20, to elucidate the role of PIK3CA mutations in CRC.Materials and Methods: A detailed literature search was performed within the PubMed, Web of Science, and Embase databases, examining the associations between PIK3CA mutations and demographic characteristics, clinicopathologic parameters, and molecular features in patients with CRC. The odds ratios with 95% confidence intervals were used to estimate the effect of PIK3CA mutations on outcome parameters.Results: Forty-four studies enrolling 17621 patients were eligible for inclusion. PIK3CA mutations were associated with proximal tumor location, mucinous differentiation, KRAS mutations, and microsatellite instability (MSI). Subgroup analysis demonstrated that PIK3CA exon 9 mutations were positively associated with proximal tumor location and KRAS mutations, and negatively associated with BRAF mutations and MSI; exon 20 mutations were associated with proximal tumor location, KRAS mutations, BRAF mutations and MSI.Conclusions: Our findings suggest that overall or exon-specific PIK3CA mutations showed null associations with key clinicopathological parameters, including disease stage and tumor differentiation, indicating that PIK3CA mutations do not predict aggressive clinicopathological characteristics in CRC. As PIK3CA mutations were found to be closely associated with KRAS mutations, their relationship warrants further investigation. Since PIK3CA exon 9 and 20 mutations showed different tendencies with regard to BRAF mutation and MSI status, they may have distinct molecular impacts on CRC.

A novel BRCA1 germline mutation promotes triple-negative breast cancer cells progression and enhances sensitivity to DNA damage agents.

Breast cancer is the most frequent malignancy and the second leading cause of cancer death in female worldwide. Compared with general population, patients with mutations in BRCA1 and BRCA2 genes confer approximately 10-fold increased risk of breast cancer. In this study, we conducted whole-exome sequencing to identify the disease-associated genes in a specific pedigree, in which at least eight individuals were diagnosed with cancers, including breast cancer, urothelial cancer, uterine cancer and colorectal cancer. Furthermore, a nonsense mutation BRCA1 p.Trp372X was identified in the proband. The Sanger sequencing data has validated the same nonsense mutation in other 4 cancer patients and 3 normal family members. Additionally, functional experiments detected that this mutation was implicated in TNBC progression, manifesting as increased cell proliferation and migration. Cells with this mutation displayed impaired recruitment of RAD51 foci and unrepaired DNA damage, potentiating drug sensitivity to PARP inhibitor and cisplatin, both in the settings of combination use or monotherapy. On the basis of its occurrence in hereditary breast cancer and its identification in pedigree, as well as its function as a disruption of BRCA1, this mutation is critical to breast cancer predisposition and progression. Patients carrying this mutation may benefit from DNA damaging treatment regimens. Conclusively, we firstly reported this nonsense mutation in family pedigree and validated its pathogenicity through in vitro functional experiments.

DAXX, as a Tumor Suppressor, Impacts DNA Damage Repair and Sensitizes BRCA-Proficient TNBC Cells to PARP Inhibitors.

Treatment options are limited for patients with triple negative breast cancer (TNBC). Understanding genes that participate in cancer progression and DNA damage response (DDR) may improve therapeutic strategies for TNBC. DAXX, a death domain-associated protein, has been reported to be critically involved in cancer progression and drug sensitivity in multiple cancer types. However, its role in breast cancer, especially for TNBC, remains unclear. Here, we demonstrated a tumor suppressor function of DAXX in TNBC proliferation, colony formation, and migration. In Mouse Xenograft Models, DAXX remarkably inhibited tumorigenicity of TNBC cells. Mechanistically, DAXX could directly bind to the promoter region of RAD51 and impede DNA damage repair, which impacted the protection mechanism of tumor cells that much depended on remaining DDR pathways for cell growth. Furthermore, DAXX-mediated inefficient DNA damage repair could sensitize BRCA-proficient TNBC cells to PARP inhibitors. Additionally, we identified that dual RAD51 and PARP inhibition with RI-1 and ABT888 significantly reduced TNBC growth both in vitro and in vivo, which provided the first evidence of combining RAD51 and PARP inhibition in BRCA-proficient TNBC. In conclusion, our data support DAXX as a modulator of DNA damage repair and suppressor of TNBC progression to sensitize tumors to the PARP inhibitor by repressing RAD51 functions. These provide an effective strategy for a better application of PARP inhibition in the treatment of TNBC.

Combined Androgen receptor blockade overcomes the resistance of breast cancer cells to palbociclib.

The dysregulation of cyclin D -Cyclin-dependent kinase 4/6 (CDK4/6)-Rb axis has been implicated in breast cancer progression and the selective CDK4/6 inhibitors have shown effective activity in advanced breast cancer, especially in tumors driven by the estrogen receptor (ER). However, resistance to these small molecular inhibitors has become an inevitable clinical issue after their initial use. Here, we investigated the potential mechanism of resistance by establishing a CDK4/6 inhibitor palbociclib-resistant breast cancer cell line (MCF-7pR). After prolonged exposure to palbociclib, we detected the loss of the ER signaling and an increase in androgen receptor (AR). Moreover, we demonstrated more localization of AR in the cell nucleus of MCF-7pR compared to the parental cell (MCF-7). We also reported that AR could promote the progression of the cell cycle. Blockade of AR signaling could reduce the level of the relative G1-S cyclins, abolish Rb phosphorylation and inhibit the activation of transcriptional programs in S phase. Furthermore, dual inhibition of AR and CDK4/6 could reverse the resistance of palbociclib both in vitro and in vivo. In sum, our studies provide evidence that AR activation promotes cell cycle progression and cell proliferation in CDK4/6 inhibitor resistance, and identify AR inhibition as a putative novel therapeutic strategy to treat CDK4/6 inhibitor resistance in cancer.

Therapeutic landscape in mutational triple negative breast cancer.

Triple negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Genomic sequencing has detected a distinctive mutational portrait of both the germline and somatic alterations in TNBC, which is staggeringly different from other breast cancer subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. However, for other predisposition genes, studies concerning the risk and penetrance to TNBC are relatively scarce. Very few recurrent mutations, including TP53 and PI3KCA mutations, together with a long tail of individually rare mutations occur in TNBC. These combined effects of genomic alterations drive TNBC progression. Given the complexity and heterogeneity of TNBC, clinical interpretation of the genomic alterations in TNBC may pave a new way for the treatment of TNBC. In this review, we summarized the germline and somatic mutation profiles of TNBC and discussed the current and upcoming therapeutic strategies targeting the mutant proteins or pathways to enable tailored-therapeutics.

Emerging therapeutic modalities of PARP inhibitors in breast cancer.

Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Since the initial approval of olaparib, a mostly investigated PARP inhibitor (PARPi), the clinical development of PARPi in breast cancer treatment has been a major emphasis. Researches in investigating platinum-PARPi combination use compared with platinum monotherapy demonstrated promising benefit in metastatic BRCA mutated breast cancer or TNBC, while no such superiority was observed in the neoadjuvant setting of TNBC. Moreover, the utility of PARP inhibition in BRCA1/2 mutated breast cancer with different platinum-free interval was investigated. There was a clear association between clinical benefit with PARPi and platinum sensitivity, whereas partial efficacy of PARPi still occurs in platinum-resistant patients. In addition, proof-of-principle studies of immunotherapy combined with PARPi in breast cancer have obtained promising results, indicating the potential benefit of the combination therapy in patients with breast cancer. These efforts, contributing to maximize the utility of PARPi, may drive a new era of this agent after its first routine use. In this review, we summarized the utility of combining platinum-PARPi in BRCA mutated breast cancer or TNBC compared with platinum monotherapy and provided promising prospects of PARPi as maintenance therapy in breast cancer, as well as providing a strong rationale for testing immunotherapy combined with PARPi in breast cancer to expand the clinical utility of PARPi.

An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer.

Androgen receptor (AR) is emerging as a novel prognostic biomarker in triple-negative breast cancer (TNBC), but the underlying mechanisms remain unknown. As accumulating evidence has shown that long non-coding RNAs (lncRNAs) regulate important cancer hallmarks, we hypothesised that AR-regulated lncRNAs might play roles in TNBC progression. Here, we performed experiments with or without DHT treatment in three TNBC cell lines, and we identified an AR negatively induced lncRNA (ARNILA), which correlated with poor progression-free survival (PFS) in TNBC patients and promoted epithelial-mesenchymal transition (EMT), invasion and metastasis in vitro and in vivo. Subsequently, we demonstrated that ARNILA functioned as a competing endogenous RNA (ceRNA) for miR-204 to facilitate expression of its target gene Sox4, which is known to induce EMT and contribute to breast cancer progression, thereby promoting EMT, invasion and metastasis of TNBC. Our findings not only provide new insights into the mechanisms of lncRNA in regulating AR but also suggest ARNILA as an alternative therapeutic target to suppress metastasis of TNBC patients.