Objective: Our purpose was to study the roles and molecular mechanisms of long non-coding RNA (lncRNA) ZFPM2 Antisense RNA 1 (ZFPM2-AS1) in thyroid cancer. Methods: Firstly, the expression of ZFPM2-AS1, miR-515-5p and TUSC3 was detected in thyroid cancer tissues and cells. Secondary, their biological functions (proliferation, apoptosis, migration and invasion) were analyzed by a serious of functional experiments including cell counting kit-8 (CCK-8), clone formation, 5-Ethynyl-2\'-deoxyuridine (EdU), enzyme-linked immunosorbent assay (ELISA), wound healing and Transwell assays. Thirdly, the mechanisms of STAT1/ZFPM2-AS1 and ZFPM2-AS1/miR-515-5p/TUSC were validated using chromatin immunoprecipitation (CHIP), pull-down and luciferase reporter assays. Results: ZFPM2-AS1 and TUSC were both highly expressed and miR-515-5p was down-regulated in thyroid cancer tissues as well as cells. Their knockdown weakened thyroid cancer cell growth, migration, and invasion. ZFPM2-AS1 was mainly distributed in the nucleus and cytoplasm of thyroid cancer cells. Mechanistically, up-regulation of ZFPM2-AS1 was induced by transcription factor STAT1 in line with CHIP and luciferase reporter assays. Furthermore, as a sponge of miR-515-5p, ZFPM2-AS1 decreased the ability of miR-515-5p to inhibit TUSC3 expression by pull-down, luciferase reporter and gain-and-loss assays, thereby promoting malignant progression of thyroid cancer. Conclusion: ZFPM2-AS1 acted as an oncogene in thyroid cancer, which was transcriptionally mediated by STAT1. Furthermore, ZFPM2-AS1 weakened the inhibitory effect of miR-515-5p on TUSC3. Thus, ZFPM2-AS1 could be an underlying biomarker for thyroid cancer.

Oral tumors are malignant cancers caused by abnormal proliferation or pathological changes of soft or hard tissues in the oral cavity. Serious cases may pose a threat to life. However, its precancerous lesions remain unclear. This study is based on a comprehensive strategy to explore a multi-factor-driven oral cancer barrier module, which is an attempt to describe the pathogenesis of the disease and potential regulatory drugs from a global perspective. Functional disease modules were identified by constructing a protein-specific interaction network in patients\' oral tissues. Then, comprehensive pathogenesis was explored through combination with analysis of functional and signaling pathway enrichment, prediction of key regulatory factors. It was found that these specifically expressed proteins and their interactions often play a pivotal part in oral tumors. This is reflected in the results of functional and pathway enrichment of modulating genes, which show that they are mainly involved in various immune responses, inflammatory reactions, oral plaque, and oral ulcer-related regulatory processes. This may represent the potential pathogenesis of oral tumors. On the predictive analysis of regulators, a series of ncRNAs (including miR-590, CRNDE and miR-340) and transcription factors (including E2F1, MYC and TP53) were identified that have potential important regulatory effects on oral tumors. These key regulators may manipulate a crucial part of the module sub-network and then work together to mediate the occurrence of oral tumors. On the comprehensive Multi-omics module analysis, the specific proteins and their interactions in patients\' oral tissues were identified, while the prominent pivotal regulators were involved in the different pathogenic functions of oral tumors.

As a major threat among women globally, breast cancer (BC) emerges as a primary research focus for several researchers. Although various therapeutic regimens are available, there is an increased chance of metastasis of BC cells, which raises the severity of this malignancy. Of multiple preferred secondary targets, metastasis to bone is extensively studied. Besides deemed as a bone transcription factor, Runx2 also acts as a metastatic factor that promotes growth and metastasis of BC cells. Studies have reported the significant role of microRNAs (miRNAs) in BC pathogenesis and metastasis by governing Runx2 expression. Additionally, dysregulation of the signaling pathways, including Wnt/β-catenin, TGF-β, Notch, and PI3K/AKT, has been observed to influence the expression of Runx2 in BC cells. In this review, we have aimed to highlight the regulatory role of miRNAs in targeting Runx2 both directly and indirectly by governing respective signaling pathways during bone metastasis of BC.

BACKGROUND: Breast cancer (BC) accounts for one of the most prevalent malignancies in the world. Inflammatory molecules modulate tumor microenvironment in BC that promotes tumor growth and metastasis. NF-κB (a transcription factor) that regulates multiple immune functions and acts as a crucial mediator of inflammatory responses.
OBJECTIVE: The present study is aimed to quantitatively summarize the relation of NFKB1-94 ATTG (I, insertion/D, deletion) variant and risk of BC.
METHODS: Further, the meta-analysis includes three independent case-control investigations that focus on NFKB1-94, ATTG I/D polymorphism, and BC patients. Web of Science, PubMed and Embase databases were used to retrieve relevant data. OR and 95% confidence interval of pooled studies were analyzed by using the MetaGenyo web tool.
RESULTS: This study revealed a high heterogeneity. In all three genetic comparison models, the NFKB1-94 ATTG I/D variant is not related to the risk of BC. Further, no publication bias on the connection between NFKB1-94 ATTG I/D variant and risk of BC was observed.
CONCLUSIONS: To summarize, our meta-analysis demonstrates that the NFKB1-94 ATTG I/D polymorphism is not a major risk factor for BC.

The blood-brain barrier (BBB) is a barrier of the central nervous system (CNS), which can restrict the free exchange of substances, such as toxins and drugs, between cerebral interstitial fluid and blood, keeping the relative physiological stabilization. The brain capillary endothelial cells, one of the structures of the BBB, have a variety of ATP-binding cassette transporters (ABC transporters), among which the most widely investigated is Pglycoprotein (P-gp) that can efflux numerous substances out of the brain. The expression and activity of P-gp are regulated by various signal pathways, including tumor necrosis factor-α (TNF-α)/protein kinase C-β (PKC- β)/sphingosine-1-phosphate receptor 1 (S1P), vascular endothelial growth factor (VEGF)/Src kinase, etc. However, it remains unclear how hypoxic signaling pathways regulate the expression and activity of P-gp in brain microvascular endothelial cells. According to previous research, hypoxia affects the expression and activity of the transporter. If the transporter is up-regulated, some drugs enter the brain\'s endothelial cells and are pumped back into the blood by transporters such as P-gp before they enter the brain tissue, consequently influencing the drug delivery in CNS; if the transporter is down-regulated, the centrally toxic drug would enter the brain tissue and cause serious adverse reactions. Therefore, studying the mechanism of hypoxia-regulating P-gp can provide an important reference for the treatment of CNS diseases with a hypoxia/reoxygenation (H/R) component. This article summarized the mechanism of regulation of P-gp in BBB in normoxia and explored that of hypoxia.

BACKGROUND: Epithelial-to-Mesenchymal Transition (EMT) is necessary for metastasis. Zinc- finger domain-containing transcription factors, especially Snail1, bind to E-box motifs and play a crucial role in the induction and regulation of EMT.
OBJECTIVE: We hypothesized if C-terminal region of Snail1 (CSnail1) may competitively bind to E-box and block cancer metastasis.
METHODS: The CSnail1 gene coding sequence was inserted into the pIRES2-EGFP vector. Following transfection of A549 cells with the designed construct, EMT was induced with TGF-β1 and the expression of essential EMT markers was evaluated by real-time PCR and immunoblotting. We also monitored cell migration.
RESULTS: CSnail1 inhibited TGF-β1-induced N-cadherin and vimentin mRNA expression and increased β-catenin expression in transfected TGF-β1-treated A549 cells. A similar finding was obtained in western blotting. CSnail1 also blocked the migration of transfected cells in the scratch test.
CONCLUSIONS: Transfection of A549 cells with CSnail1 alters the expression of essential EMT markers and consequently suppresses tumor cell migration. These findings confirm the capability of CSnail1 in EMT blocking and in parallel to current patents could be applied as a novel strategy in the prevention of metastasis.

BRN2 transcription factor is associated with the development of malignant melanoma. The cytotoxic activities and cell death mechanism against B16F10-Nex2 cells were determined with synthetic peptide R18H derived from the POU domain of the BRN2 transcription factor.
To determine the cell death mechanisms and in vivo activity of peptide R18H derived from the POU domain of the BRN2 transcription factor against B16F10-Nex2 cells.
Cell viability was determined by the MTT method. C57Bl/6 mice were challenged with B16F10-Nex2 cells and treated with R18H. To identify the type of cell death, we used TUNEL assay, Annexin V and PI, Hoechst, DHE, and determination of caspase activation and cytochrome c release. Transmission electron microscopy was performed to verify morphological alterations after peptide treatment.
Peptide R18H displayed antitumor activity in the first hours of treatment and the EC50% was calculated for 2 and 24h, being 0.76 ± 0.045 mM and 0.559 ± 0.053 mM, respectively. After 24h apoptosis was evident, based on DNA degradation, chromatin condensation, increase of superoxide anion production, phosphatidylserine translocation, activation of caspases 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. The peptide cytotoxic activity was not affected by necroptosis inhibitors and treated cells did not release LDH in the extracellular medium. Moreover, in vivo antitumor activity was observed following treatment with peptide R18H.
Peptide R18H from BRN2 transcription factor induced apoptosis in B16F10-Nex2 and displayed antitumor activity in vivo.

Renal cell carcinoma (RCC) is the most common tumor of the kidney and its major histologic subtype is clear cell RCC (ccRCC). About 30% of diagnosed ccRCCs already have metastasis. Traditionally, localized ccRCC is treated with nephrectomy but the relapse rate is 30%. Thus, the discovery of effective biomarkers for early detection, as well as the identification of new targets for molecular-based therapy of ccRCC are urgently required. In this study, we focused on molecules that could modulate the trascription of the enzyme nicotinamide N-methyltransferase (NNMT) that is known to be up-regulated in ccRCC. Signal transducer and activator of transcription 3 (STAT3), interleukin 6 (IL-6), hepatocyte nuclear factor 1 beta (HNF-1β) and transforming growth factor beta 1 (TGF-β1) expression levels were determined in tumor and non tumor samples obtained from 30 patients with ccRCC, using Real-Time PCR. Results obtained showed that TGF-β1 is significantly (p<0.05) overexpressed in tumor compared with normal tissue samples of ccRCC patients. Conversely, we did not find any statistically significant difference concerning STAT3, IL-6, HNF-1β gene expression levels. TGF-β1 up-regulation could be responsible for the high levels of NNMT observed in ccRCC. Targeting TGF-β1 could improve the outcome of ccRCC patients due to its role in epithelial-mesenchymal transition (EMT), that is known to be associated with a worse overall survival (OS) in this neoplasm.

Clusterin is a multifunctional glycoprotein whose role in cells has generated a great controversy in recent years. Since its discovery, numerous studies have linked clusterin expression deregulation with various physio-pathological processes such as cancer or Alzheimer\'s disease. Although the results of such investigations have sometimes been contradictory, mainly due to the dichotomous role of clusterin isoforms, it has been demonstrated that this protein is involved in diverse cellular processes, including apoptosis, cell cycle regulation, DNA repair or the acquisition of cell resistance against multiple conventional therapies. These results, together with the breakthrough of gene therapies, have motivated a great effort to elucidate the importance of clusterin as a potential therapeutic target. However, the understanding of a single gene, with multiple RNA transcripts and several protein isoforms has turned out to be a complex task. In this review, we summarize the studies published to date on factors that can affect clusterin expression and evaluate if a better understanding of this complex gene/protein would be useful to develop new treatment strategies for cancer and other pathologies.

FUSCA3 (FUS3) is a short-lived B3-domain transcription factor that regulates seed development and phase transitions in Arabidopsis thaliana. The mechanisms controlling FUS3 levels are currently poorly understood. Here we show that FUS3 interacts with the RING E3 ligase ABI3-INTERACTING PROTEIN2 (AIP2). AIP2-green fluorescent protein (GFP) is preferentially expressed in the protoderm during early embryogenesis, similarly to FUS3, suggesting that their interaction is biologically relevant. FUS3 degradation is delayed in the aip2-1 mutant and FUS3-GFP fluorescence is increased in aip2-1, but only during mid-embryogenesis, suggesting that FUS3 is negatively regulated by AIP2 at a specific time during embryogenesis. aip2-1 shows delayed flowering and therefore also functions post-embryonically to regulate developmental phase transitions. Plants overexpressing FUS3 post-embryonically in the L1 layer (ML1p:FUS3) show late flowering and other developmental phenotypes that can be rescued by ML1p:AIP2, further supporting a negative role for AIP2 in FUS3 accumulation. However, additional factors regulate FUS3 levels during embryogenesis, as ML1:AIP2 seeds do not resemble fus3-3. Lastly, targeted expression of a RING-inactive AIP2 variant to the protoderm/L1 layer causes FUS3 and ABI3 overexpression phenotypes and defects in cotyledon development. Taken together, these results indicate that AIP2 targets FUS3 for degradation and plays a role in cotyledon development and flowering time in Arabidopsis.