Commiphora gileadensis and C. foliacea (family Burseraceae) are pantropical in nature and known for producing fragrant resin (myrrh). Both the tree species are economically and medicinally important however, least genomic understanding is available for this genus. Herein, we report the complete chloroplast genome sequences of C. gileadensis and C. foliacea and comparative analysis with related species (C. wightii and Boswellia sacra). A modified chloroplast DNA extraction method was adopted, followed with next generation sequencing, detailed bioinformatics and PCR analyses. The results revealed that the cp genome sizes of C. gileadensis and C. foliacea, are 160,268 and 160,249 bp, respectively, with classic quadripartite structures that comprises of inverted repeat’s pair. Overall, the organization of these cp genomes, GC contents, gene order, and codon usage were comparable to other cp genomes in angiosperm. Approximately, 198 and 175 perfect simple sequence repeats were detected in C. gileadensis and C. foliacea genomes, respectively. Similarly, 30 and 25 palindromic, 15 and 25 forward, and 20 and 25 tandem repeats were determined in both the cp genomes, respectively. Comparison of these complete cp genomes with C. wightii and B. sacra revealed significant sequence resemblance and comparatively highest deviation in intergenic spacers. The phylo-genomic comparison showed that C. gileadensis and C. foliacea form a single clade with previously reported C. wightii and B. sacra from family Burseraceae. Current study reports for the first time the cp genomics of species from Commiphora, which could be helpful in understanding genetic diversity and phylogeny of this myrrh producing species.

Circulating tumor cell clusters (CTCcl) have a higher metastatic potential compared to single CTCs and predict long-term outcomes in breast cancer (BC) patients. Because of the rarity of CTCcls, molecular characterization of primary tumors that give rise to CTCcl hold significant promise for better diagnosis and target discovery to combat metastatic BC. In our study, we utilized the reverse-phase protein array (RPPA) and transcriptomic (RNA-Seq) data of 10 triple-negative BC patient-derived xenograft (TNBC PDX) transplantable models with CTCs and evaluated expression of upregulated candidate protein Bcl2 (B-cell lymphoma 2) by immunohistochemistry (IHC). The sample-set consisted of six CTCcl-negative (CTCcl−) and four CTCcl-positive (CTCcl+) models. We analyzed the RPPA and transcriptomic profiles of CTCcl− and CTCcl+ TNBC PDX models. In addition, we derived a CTCcl-specific gene signature for testing if it predicted outcomes using a publicly available dataset from 360 patients with basal-like BC. The RPPA analysis of CTCcl+ vs. CTCcl− TNBC PDX tumors revealed elevated expression of Bcl2 (false discovery rate (FDR) < 0.0001, fold change (FC) = 3.5) and reduced acetyl coenzyme A carboxylase-1 (ACC1) (FDR = 0.0005, FC = 0.3) in CTCcl+ compared to CTCcl− tumors. Genome-wide transcriptomic analysis of CTCcl+ vs. CTCcl− tumors revealed 549 differentially expressed genes associated with the presence of CTCcls. Apoptosis was one of the significantly downregulated pathways (normalized enrichment score (NES) = −1.69; FDR < 0.05) in TNBC PDX tumors associated with CTCcl positivity. Two out of four CTCcl+ TNBC PDX primary tumors had high Bcl2 expression by IHC (H-score > 34); whereas, only one of six CTCcl− TNBC PDX primary tumors met this criterion. Evaluation of epithelial-mesenchymal transition (EMT)-specific signature did not show significant differences between CTCcl+ and CTCcl− tumors. However, a gene signature associated with the presence of CTCcls in TNBC PDX models was associated with worse relapse-free survival in the publicly available dataset from 360 patients with basal-like BC. In summary, we identified the multigene signature of primary PDX tumors associated with the presence of CTCcls. Evaluation of additional TNBC PDX models and patients can further illuminate cellular and molecular pathways facilitating CTCcl formation.

Teucrium is one of the most economically and ecologically important genera in the Lamiaceae family; however, it is currently the least well understood at the plastome level. In the current study, we sequenced the complete chloroplast (cp) genomes of T. stocksianum subsp. stenophyllum R.A.King (TSS), T. stocksianum subsp. stocksianum Boiss. (TS) and T. mascatense Boiss. (TM) through next-generation sequencing and compared them with the cp genomes of related species in Lamiaceae (Ajuga reptans L., Caryopteris mongholica Bunge, Lamium album L., Lamium galeobdolon (L.) Crantz, and Stachys byzantina K.Koch). The results revealed that the TSS, TS and TM cp genomes have sizes of 150,087, 150,076 and 150,499 bp, respectively. Similarly, the large single-copy (LSC) regions of TSS, TS and TM had sizes of 81,707, 81,682 and 82,075 bp, respectively. The gene contents and orders of these genomes were similar to those of other angiosperm species. However, various differences were observed at the inverted repeat (IR) junctions, and the extent of the IR expansion into ψrps19 was 58 bp, 23 bp and 61 bp in TSS, TS and TM, respectively. Similarly, in all genomes, the pbsA gene was present in the LSC at varying distances from the JLA (IRa-LSC) junction. Furthermore, 89, 72, and 92 repeats were identified in the TSS, TM and TS cp genomes, respectively. The highest number of simple sequence repeats was found in TSS (128), followed by TS (127) and TM (121). Pairwise alignments of the TSS cp genome with related cp genomes showed a high degree of synteny. However, relatively lower sequence identity was observed when various coding regions were compared to those of related cp genomes. The average pairwise divergence among the complete cp genomes showed that TSS was more divergent from TM (0.018) than from TS (0.006). The current study provides valuable genomic insight into the genus Teucrium and its subspecies that may be applied to a more comprehensive study.

G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain unexplored in breast cancer (BC). We interrogated the expression and phosphorylation status of 398 non-sensory GPCRs using the landmark BC proteogenomics and phosphoproteomic dataset from The Cancer Genome Atlas. Neuropeptide Y Receptor Y1 (NPY1R) gene and protein expression were significantly higher in Luminal A tumors versus other BC subtypes. The trend of NPY1R gene, protein, and phosphosite (NPY1R-S368s) expression was decreasing in the order of Luminal A, Luminal B, Basal, and human epidermal growth factor receptor 2 (HER2) subtypes. NPY1R gene expression increased in response to estrogen and reduced with endocrine therapy in estrogen receptor-positive (ER+) BC cells and xenograft models. Conversely, NPY1R expression decreased in ER+ BC cells resistant to endocrine therapies (estrogen deprivation, tamoxifen, and fulvestrant) in vitro and in vivo. NPY treatment reduced estradiol-stimulated cell growth, which was reversed by NPY1R antagonist (BIBP-3226) in ER+ BC cells. Higher NPY1R gene expression predicted better relapse-free survival and overall survival in ER+ BC. Our study demonstrates that NPY1R mediates the inhibitory action of NPY on estradiol-stimulated growth of ER+ BC cells, and its expression serves as a biomarker to predict endocrine sensitivity and survival in ER+ BC patients.

While G protein‐coupled receptors (GPCRs) are known to be excellent drug targets, the second largest family of adhesion‐GPCRs is less explored for their role in health and disease. ADGRF1 (GPR110) is an adhesion‐GPCR and has an important function in neurodevelopment and cancer. Despite serving as a poor predictor of survival, ADGRF1’s coupling to G proteins and downstream pathways remain unknown in cancer. We evaluated the effects of ADGRF1 overexpression on tumorigenesis and signaling pathways using two human epidermal growth factor receptor‐2‐positive (HER2+) breast cancer (BC) cell‐line models. We also interrogated publicly available clinical datasets to determine the expression of ADGRF1 in various BC subtypes and its impact on BC‐specific survival (BCSS) and overall survival (OS) in patients. ADGRF1 overexpression in HER2+ BC cells increased secondary mammosphere formation, soft agar colony formation, and % of Aldefluor‐positive tumorigenic population in vitro and promoted tumor growth in vivo. ADGRF1 co‐immunoprecipitated with both Gαs and Gαq proteins and increased cAMP and IP1 when overexpressed. However, inhibition of only the Gαs pathway by SQ22536 reversed the pro‐tumorigenic effects of ADGRF1 overexpression. RNA‐sequencing and RPPA analysis revealed inhibition of cell cycle pathways with ADGRF1 overexpression, suggesting cellular quiescence, as also evidenced by cell cycle arrest at the G0/1 phase and resistance to chemotherapy in HER2+ BC. ADGRF1 was significantly overexpressed in the HER2‐enriched BC compared to luminal A and B subtypes and predicted worse BCSS and OS in these patients. Therefore, ADGRF1 represents a novel drug target in HER2+ BC, warranting discovery of novel ADGRF1 antagonists.