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Purpose: This study aims to explore the role of circ_0032704 in sorafenib‐resistant hepatocellular carcinoma (HCC). Methods: The expression of circ_0032704, miR‐514a‐3p, and programmed death‐ligand 1 (PD‐L1) mRNA was detected by quantitative real‐time PCR (qPCR). The expression of multidrug resistant‐related proteins, migration/invasion‐related proteins, exosome‐related proteins, and PD‐L1 protein was detected by western blot. Cell viability was detected by CCK‐8 assay. Cell proliferation, migration, and invasion were assessed by EdU assay, wound healing assay, and transwell assay. The binding between miR‐514a‐3p and circ_0032704 or PD‐L1 was verified by RIP assay, pull‐down assay, and dual‐luciferase reporter assay. Cell‐ or serum‐derived exosomes were isolated and identified by TEM and NTA. Xenograft models were established to determine the effect of circ_0032704 on drug resistance in vivo. Results: Circ_0032704 was overexpressed in sorafenib‐resistant HCC tissues and cells. Circ_0032704 knockdown reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib‐resistant HCC cells, while these effects were reversed by PD‐L1 overexpression. We found that circ_0032704 positively regulated PD‐L1 expression via targeting miR‐514a‐3p. Exosomes with circ_0032704 inhibition reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib‐resistant HCC cells. Exosomes with circ_0032704 inhibition also inhibited tumor growth in vivo. The expression of circ_0032704 in exosomes was stable and possessed diagnostic value. Conclusion: Circ_0032704 enhanced sorafenib resistance in HCC and promoted the malignant development of sorafenib‐resistant HCC. Circ_0032704 could be transported by exosomes, and exosomal circ_0032704 had diagnostic value. [ABSTRACT FROM AUTHOR]

The starch synthase (SS) plays important roles in regulating plant growth and development and responding to adversity stresses. Although the SS family has been studied in many crops, it has not been fully identified in sweet potato and its two related species. In the present study, eight SSs were identified from Ipomoea batatas (I. batata), Ipomoea trifida (I. trifida), and Ipomoea trlioba (I. trlioba), respectively. According to the phylogenetic relationships, they were divided into five subgroups. The protein properties, chromosomal location, phylogenetic relationships, gene structure, cis-elements in the promoter, and interaction network of these proteins were also analyzed; stress expression patterns were systematically analyzed; and real-time polymerase chain reaction (qRT-PCR) analysis was performed. Ipomoea batatas starch synthase (IbSSs) were highly expressed in tuber roots, especially Ipomoea batatas starch synthase 1 (IbSS1) and Ipomoea batatas starch synthase 6 (IbSS6), which may play an important role in root development and starch biosynthesis. At the same time, the SS genes respond to potassium deficiency, hormones, cold, heat, salt, and drought stress. This study offers fresh perspectives for enhancing knowledge about the roles of SSs and potential genes to enhance productivity, starch levels, and resistance to environmental stresses in sweet potatoes. [ABSTRACT FROM AUTHOR]

The LBD family is a plant-specific transcription factor family that plays an important role in a variety of biological processes. However, the function of IbLBD genes in sweet potato remains unclear. In this study, we identified a total of 53 IbLBD genes in sweet potato. Genetic structure showed that most of the IbLBD genes contained only two exons. Following the phylogenetic investigation, the IbLBD gene family was separated into Class I (45 members) and Class II (8) members. Both classes of proteins contained relatively conservative Motif1 and Motif2 domains. The chromosomal locations, gene duplications, promoters, PPI network, and GO annotation of the sweet potato LBD genes were also investigated. Furthermore, gene expression profiling and real-time quantitative PCR analysis showed that the expression of 12 IbLBD genes altered in six separate tissues and under various abiotic stresses. The IbLBD genes belonging to Class I were mostly expressed in the primary root, the pencil root, and the leaves of sweet potatoes, while the genes belonging to Class II were primarily expressed in the various sweet potato roots. The IbLBD genes belonging to Class I were mostly expressed in the primary root, the pencil root, and the leaves of sweet potatoes, while the genes belonging to Class II were primarily expressed in the fibrous root, pencil root, and tuber root. [ABSTRACT FROM AUTHOR]

Background: Cytochrome P450 monooxygenases (CYP450s) play a crucial role in various biochemical reactions involved in the synthesis of antioxidants, pigments, structural polymers, and defense-related compounds in plants. As sweet potato (Ipomoea batatas L.) holds significant economic importance, a comprehensive analysis of CYP450 genes in this plant species can offer valuable insights into the evolutionary relationships and functional characteristics of these genes. Results: In this study, we successfully identified and categorized 95 CYP450 genes from the sweet potato genome into 5 families and 31 subfamilies. The predicted subcellular localization results indicate that CYP450s are distributed in the cell membrane system. The promoter region of the IbCYP450 genes contains various cis-acting elements related to plant hormones and stress responses. In addition, ten conserved motifs (Motif1-Motif10) have been identified in the IbCYP450 family proteins, with 5 genes lacking introns and only one exon. We observed extensive duplication events within the CYP450 gene family, which may account for its expansion. The gene duplication analysis results showed the presence of 15 pairs of genes with tandem repeats. Interaction network analysis reveals that IbCYP450 families can interact with multiple target genes and there are protein-protein interactions within the family. Transcription factor interaction analysis suggests that IbCYP450 families interact with multiple transcription factors. Furthermore, gene expression analysis revealed tissue-specific expression patterns of CYP450 genes in sweet potatoes, as well as their response to abiotic stress and plant hormones. Notably, quantitative real-time polymerase chain reaction (qRT‒PCR) analysis indicated the involvement of CYP450 genes in the defense response against nonbiological stresses in sweet potatoes. Conclusions: These findings provide a foundation for further investigations aiming to elucidate the biological functions of CYP450 genes in sweet potatoes. [ABSTRACT FROM AUTHOR]

Malate dehydrogenase (MDH; EC 1.1.1.37) plays a vital role in plant growth and development as well as abiotic stress responses, and it is widely present in plants. However, the MDH family genes have not been explored in sweet potato. In this study, nine, ten, and ten MDH genes in sweet potato (Ipomoea batatas) and its two diploid wild relatives, Ipomoea trifida and Ipomoea triloba, respectively, were identified. These MDH genes were unevenly distributed on seven different chromosomes among the three species. The gene duplications and nucleotide substitution analysis (Ka/Ks) revealed that the MDH genes went through segmental duplications during their evolution under purifying selection. A phylogenetic and conserved structure divided these MDH genes into five subgroups. An expression analysis indicated that the MDH genes were omni-presently expressed in distinct tissues and responded to various abiotic stresses. A transcription factor prediction analysis proved that Dof, MADS-box, and MYB were the main transcription factors of sweet potato MDH genes. These findings provide molecular features of the MDH family in sweet potato and its two diploid wild relatives, which further supports functional characterizations. [ABSTRACT FROM AUTHOR]

Background. It is well known that cancer stem cells can induce cancer metastasis, which causes the majority of cancer-related death, especially in triple-negative breast cancer (TNBC). TNBC features a high metastatic rate and low metastasis-free survival and is regarded as the most malignant subtype of breast cancer. The purpose of this study is to explore prognostic biomarkers that can predict metastasis of triple-negative breast cancer. Methods. The human triple-negative breast cancerSUM149PT cells were used for the study. The cancer stem cell spheres (sum149-Stem) and paired adherent cancer cells (sum149-Tumor) were collected to extract total RNAs. RNA-seq was used to analysis the mRNA expression of cancer stem cells and paired adherent cancer cells. Two different gene expression omnibus datasets (https://www.ncbi.nlm.nih.gov/gds), GSE58812 and GSE33926, were used to explore the mechanism of different expression genes between stem cells and adherent cancer cells. Seven genes showed prognostic function in all datasets. The STITCH database (https://www.stitchdata.com/) was used to explore the possible metastasis-inhibiting drugs that can target the seven genes. Each gene expression was compared by Pearson analysis. The receiver operating characteristic curve (ROC) and Kaplan–Meier survival curve were performed to assess the metastasis prognostic ability of the seven-gene modeling two different GEO datasets. Results. A subset of 7 stemness-related genes (SRGs) containing UCN, ST3GAL5, FDPS, HK2, MALL, LMTK3, and CRHR2 were identified in three independent cohorts. Univariate Cox analysis showed that ST3GAL5 plays an antitumor role in TNBC metastasis, and the other 6 genes promote the metastatic progression of TNBC. The ability of the 7-SRGs gene Cox model to predict TNBC metastasis was constructed with the GSE58812 dataset. Most of the genes showed significant expression in patients with different risk levels. Additionally, the model showed predictive value in another GEO dataset of TNBC patients. ROC curves indicated that the seven-gene model has a significant predictive value of TNBC metastasis. Conclusions. Expression analysis of the 7-SRGs signature model at diagnosis has predictive value for metastasis in TNBC patients. [ABSTRACT FROM AUTHOR]

Background: Cancer metastasis is still a life threat to patients with colorectal cancer (CRC). Brain and muscle ARNT‐like protein 1 (BMAL1) is an important biological proteins that can regulate the behavior of cancer cells and their response to chemotherapy. However, the role of BMAL1 in the tumorigenic phenotype of CRC remains unclear. Here, we aim to investigate the functional role and mechanisms of BMAL1 in CRC. Methods: The mRNA expression of BMAL1 was studied using the Cancer Genome Atlas (TCGA) databases. The protein level in clinical tissues was confirmed by immunohistochemistry (IHC). The effects of BMAL1 on the epithelial‐to‐mesenchymal transition (EMT) and proliferation of CRC cell lines (including BMAL1 overexpressed or silencing cells) were studied by Transwell, wound healing, CCK‐8 and colony formation experiments. A series of experiments were conducted to demonstrate the mechanisms of BMAL1 regulating EMT and cancer proliferation in vitro and in vivo. Results: We found that BMAL1 expression was closely related to the poor prognosis of CRC. BMAL1 overexpression promoted cell proliferation and migration. Mechanistically, we found that BMAL1 may activate the epithelial‐to‐mesenchymal transition (EMT) pathway and induce the β‐catenin release further promotes the expression of oncogene c‐Myc and the migration of colorectal cells by activating MAPK pathway. However, BMAL1 silencing achieved the opposite effect. In addition, blocking MAPK‐signaling pathway with specific inhibitors of ERK1/2 and JNK can also downregulate the expressions of c‐Myc in vitro. Taken together, these results suggested that the BMAL1/ c‐Myc‐signaling pathway may regulate the metastasis of CRC through the JNK/ERK1/2 MAPK‐dependent pathway. Conclusions: Our study showed that BMAL1 promotes CRC metastasis through MAPK‐c‐Myc pathway. These results deepen our understanding of the relationship between BMAL1 and tumorigenic phenotypes, which may become a promising therapeutic target for BMAL1 overexpressing CRC. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common form of endocrine cancer around the world, and among which papillary thyroid carcinoma (PTC) is the most ubiquitous pathological sub-kind. Sushi repeat-containing protein X-linked 2 (SRPX2) was reported to be an independent prognostic factor and significantly overexpressed in advanced PTC patients. However, the biological functions of SRPX2 remain ambiguous in PTC. Here, we explored SRPX2 expression profiles and functions in PTC, finding that SRPX2 expression was remarkably upregulated in PTC tissues and cell lines. Further colony formation, CCK-8, as well as transwell assay, suggested that SRPX2 silencing remarkably dampened PTC growth and migration. Mouse xenograft models were established to find that SRPX2 silence remarkably suppressed PTC proliferation and migration in vivo. Following mechanism studies revealed that SRPX2 realized its functions in the PTC process partially through activating the Focal adhesion kinase (FAK) phosphorylation. In conclusion, this study investigated the functions and mechanisms of the SRPX2/FAK pathway in PTC progression. SRPX2 could act as a prospective biologic signature and therapeutic target molecule for PTC. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most prevalent malignancies in the digestive system across the world. The function and mechanism of PDLIM1, a cancer-suppressing gene, in gastric cancer progression remain unclear. This study is aimed at investigating the expression features and function of PDLIM1 in GC. RT-qPCR and western blot were used to compare the profiles of PDLIM1 and miR-187 between GC and normal tissues. The cell models of PDLIM1 overexpression and low expression were established in gastric cancer cell lines MKN45 and AGS. CCK8 and BrdU assays measured cell proliferation. Flow cytometry monitored cell apoptosis. Transwell analyzed cell invasion and migration. The influence of miR-187 overexpression on gastric cancer development was assessed. We predicted the targeted correlation between miR-187 and PDLIM1 through bioinformatics, which was corroborated via dual luciferase activity assay and RIP. Meanwhile, the cell model of PDLIM1 overexpression was built in AGS cells transfected with miR-187 mimics. A rescue experiment was conducted to assess the impact of PDLIM1 overexpression on the procancer function of miR-187. As a result, in contrast with normal paracancer tissues, PDLIM1 was substantially downregulated in GC tissues. Moreover, PDLIM1 overexpression considerably dampened proliferation, invasion, and migration in GC cells, boosted the cell apoptosis, and bolstered their sensitivity to cisplatin. PDLIM1 knockdown or miR-187 overexpression dramatically fostered GC cell proliferation, invasion, and migration and repressed cell apoptosis. Mechanism studies demonstrated that PDLIM1 vigorously restrained the profiles of the Hippo-YAP signaling pathway and the downstream target genes. miR-187 targeted PDLIM1, while miR-187 overexpression cramped PDLIM1 expression. The rescue experiment suggested that PDLIM1 overexpression weakened the procancer function of miR-187 in GC cells. In conclusion, our study demonstrated that PDLIM1 presented a low expression in GC tissues, while miR-187/PDLIM1 participated in GC development and cisplatin sensitivity by mediating the Hippo-YAP signaling pathway. [ABSTRACT FROM AUTHOR]

• F-box genes are among the most abundant functionally diverse plant-specific TFs. • F-box genes regulate several developmental processes in plants. • Genome-wide characterization yielded 243F-box genes in sweet potato. • Segmental duplication is the principal factor influencing the evolution of the IbFBX genes. • IbFBX genes exhibit differential expression patterns in response to abiotic stress. In this study, genome-wide characterization of F-box proteins in sweet potato yielded 243 IbFBX genes, unevenly distributed on the 15 chromosomes of sweet potato. Gene duplication analysis suggested segmental duplication as the principal factor influencing the expansive evolution of IbFBX genes in sweet potato. Phylogenetic analysis clustered F-box proteins in sweet potato, Arabidopsis , and rice into six clades (I-VI). Gene structure analysis of the IbFBX genes revealed that most of the genes within the same clade were highly conserved. Expression profiles of IbFBX family genes in 9 different tissues and under stress conditions revealed that the IbFBXs were highly upregulated or downregulated in response to salt and drought stress, suggesting their significant roles in abiotic stress response and adaptation. Knowledge of the diverse functions and expression patterns of IbFBXs presents a solid theoretical basis for annotating the functions of IbFBXs and further facilitate the molecular breeding of sweet potato. [ABSTRACT FROM AUTHOR]