Effect of Comfort Care on Perioperative Outcomes and Postoperative Recovery of Breast Cancer Patients.

Objective: The objective of this study was to evaluate the effects of comfort care on perioperative outcomes and postoperative recovery of breast cancer patients. Evaluating comfort care is important in the context of breast cancer surgery because it can potentially alleviate pain, improve patient comfort, enhance postoperative recovery, and reduce complications, ultimately leading to better patient outcomes. Methods: Between March 2020 and December 2021, 78 patients undergoing breast cancer surgery at our hospital were randomly assigned to receive either routine nursing (routine group) or comfort care (experimental group). The comfort care intervention included various components such as health education, preoperative care, intraoperative care, postoperative care, pain care, and psychological care. The routine group received standard nursing care following medical advice. Results: The patient characteristics between the two groups were comparable. Comfort care resulted in significantly higher visual analog scale (VAS) scores, indicating reduced pain, and better improvement in functional recovery of the upper limb compared to routine nursing. Comfort care was also associated with better postoperative recovery, as evidenced by lower self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores. The experimental group had a significantly lower incidence of complications compared to the routine group. Additionally, the experimental group reported better 24-hour comfort and higher nursing satisfaction. Conclusion: In conclusion, comfort care effectively reduces postoperative pain, promotes postoperative recovery, improves patient emotions, lowers the incidence of complications, and enhances comfort and care satisfaction in breast cancer patients undergoing radical surgery. These findings highlight the importance of incorporating comfort care interventions in the perioperative management of breast cancer patients. Further research and implementation of comfort care strategies may have implications for improving clinical practice and patient outcomes in the future.

Interaction between CASP8AP2 and ZEB2-CtBP2 Regulates the Expression of LEF1.

Low expression of CTBP2 and CASP8AP2 correlated with poor outcome and predicted risk of relapse in pediatric B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to investigate the molecular mechanism by which CASP8AP2 regulates LEF1 expression by interacting with CtBP2 and ZEB2 in Acute lymphoblastic lymphoma (ALL). There was an interaction between CASP8AP2, ZEB2, and CtBP2, and then the interaction between CtBP2 and ZEB2 was observed after downregulating the expression of CASP8AP2. The wild type (containing the ZEB2 binding site) or mutant (containing a mutant binding site) LEF1 gene promoter sequence was inserted into the pGL3-basic plasmid, and a dual-luciferase reporter gene detection system was used to observe how CASP8AP2, ZEB2, and CtBP2 regulate the transcription of the LEF1 gene. We conclude that CASP8AP2, CtBP2, and ZEB2 can all bind to the LEF1 gene promoter region and reduce the luciferase activity of the LEF1 promoter. Meanwhile, the interaction of ZEB2 and the LEF1 promoter was significantly weakened after downregulation of CASP8AP2. Knockdown of CASP8AP2 in the 697 cell lines resulted in the significant upregulation of the mRNA expression levels of the stemness-related genes CD44, JAG1, and SALL4. In conclusion, CASP8AP2 is vital for the interaction between CtBP2 and ZEB2, inhibiting LEF1 and stemness-related genes expression ALL.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2033369 .

Oyster peptide prevents the occurrence of exercise-hypogonadal male condition by improving the function of pituitary gonadal axis in male rats.

This study evaluates the protective role of oyster peptide (OP) on the occurrence of Exercise-Hypogonadal Male Condition. Male rats were given heavy-load swimming training and / or OP was supplemented for 6 consecutive weeks. After heavy-load training, sperm count, sperm viability and sperm motility in epididymis, testosterone in serum and testis, glutathione peroxidase (GSH-px) and androgen receptor (AR) in testis and mating times were remarkably decreased, malondialdehyde (MDA), capture latency and mating latency were significantly increased, mRNA expression of steroidogenic acute regulatory (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc) were obviously down-regulated, but serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) were not statistically changed. Conversely, when OP was supplemented at heavy-load training, sperm count, sperm viability and sperm motility in epididymis, serum FSH, LH, testosterone, GSH-px, superoxide dismutase (SOD), testosterone, AR in testis and mating times were dramatically increased, while testicular MDA, capture latency and mating latency were significantly decreased, and mRNA expression of StAR, StARD7, P450scc and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were significantly up-regulated. In conclusion, heavy-load training causes testicular spermatogenic and steroidogenic disorders by enhancing the generation of reactive oxygen species (ROS), which can be protected by the co-administration of OP by enhancing the function of pituitary gonad axis and lowering ROS generation.

PP2A inhibition by LB-100 protects retinal pigment epithelium cells from UV radiation via activation of AMPK signaling.

AMP-activated protein kinase (AMPK) signaling activation can inhibit Ultra-violet (UV) radiation (UVR)-induced retinal pigment epithelium (RPE) cell injuries. LB-100 is a novel inhibitor of protein phosphatase 2A (PP2A), the AMPKα1 phosphatase. Here, our results demonstrated that LB-100 significantly inhibited UVR-induced viability reduction, cell death and apoptosis in established ARPE-19 cells and primary murine RPE cells. LB-100 activated AMPK, nicotinamide adenine dinucleotide phosphate (NADPH) and Nrf2 (NF-E2-related factor 2) signalings, inhibiting UVR-induced oxidative injuries and DNA damage in RPE cells. Conversely, AMPK inhibition, by AMPKα1-shRNA, -CRISPR/Cas9 knockout or -T172A mutation, almost blocked LB-100-induced RPE cytoprotection against UVR. Importantly, CRISPR/Cas9-mediated PP2A knockout mimicked and nullified LB-100-induced anti-UVR activity in RPE cells. Collectively, these results show that PP2A inhibition by LB-100 protects RPE cells from UVR via activation of AMPK signaling.

DNA Damage-Response Pathway Heterogeneity of Human Lung Cancer A549 and H1299 Cells Determines Sensitivity to 8-Chloro-Adenosine.

Human lung cancer H1299 (p53-null) cells often display enhanced susceptibility to chemotherapeutics comparing to A549 (p53-wt) cells. However, little is known regarding to the association of DNA damage-response (DDR) pathway heterogeneity with drug sensitivity in these two cells. We investigated the DDR pathway differences between A549 and H1299 cells exposed to 8-chloro-adenosine (8-Cl-Ado), a potential anticancer drug that can induce DNA double-strand breaks (DSBs), and found that the hypersensitivity of H1299 cells to 8-Cl-Ado is associated with its DSB overaccumulation. The major causes of excessive DSBs in H1299 cells are as follows: First, defect of p53-p21 signal and phosphorylation of SMC1 increase S phase cells, where replication of DNA containing single-strand DNA break (SSB) produces more DSBs in H1299 cells. Second, p53 defect and no available induction of DNA repair protein p53R2 impair DNA repair activity in H1299 cells more severely than A549 cells. Third, cleavage of PARP-1 inhibits topoisomerase I and/or topoisomerase I-like activity of PARP-1, aggravates DNA DSBs and DNA repair mechanism impairment in H1299 cells. Together, DDR pathway heterogeneity of cancer cells is linked to cancer susceptibility to DNA damage-based chemotherapeutics, which may provide aid in design of chemotherapy strategy to improve treatment outcomes.

Prediction of phosphorylation sites based on Krawtchouk image moments.

Protein phosphorylation is one of the most pervasive post-translational modifications and regulates diverse cellular processes in organisms. Under the catalysis of protein kinases, protein phosphorylation usually occurred in the residues serine (S), threonine (T), or tyrosine (Y). In this contribution, we proposed a novel scheme (named KMPhos) for the theoretical prediction of protein phosphorylation sites. First, the numerical matrix was obtained from a protein sequence fragment by replacing the characters of the residues with the chemical descriptors of amino acid molecules to approximately describe the chemical environment of the protein fragment, which was turned to the grayscale image. Then the Krawtchouk image moments were calculated and used to establish the support vector machine models. The accuracies of 10-fold cross validation for the obtained models on the training set are up to 89.7%, 88.6%, and 90.1% for the residues S, Y, and T, respectively. For the independent test set, the prediction accuracies are up to 90.7% (S), 87.8% (T), and 89.3% (Y). The results of ROC and other evaluations are also satisfactory. Compared with several specialized prediction tools, KMPhos provided the higher accuracy and reliability. An available KMPhos package is provided and can be used directly for phosphorylation sites prediction.

MiR-509-3-5p causes aberrant mitosis and anti-proliferative effect by suppression of PLK1 in human lung cancer A549 cells.

MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression and play roles in DNA damage response (DDR). PLK1 is identified as a modulator of DNA damage checkpoint. Although down-regulation of PLK1 by certain microRNAs has been reported, little is known about the interplay between PLK1 and miR-509-3-5p in DDR. Here we have demonstrated that miR-509-3-5p repressed PLK1 expression by targeting PLK1 3'-UTR, thereby causing mitotic aberration and growth arrest of human lung cancer A549 cells. Repression of PLK1 by miR-509-3-5p was further evidenced by over-expression of miR-509-3-5p in A549, HepG2 and HCT116p53(-/-) cancer cells, in which PLK1 protein was suppressed. Consistently, miR-509-3-5p was stimulated, while PLK1 protein was down-regulated in A549 cells exposed to CIS and ADR, suggesting that suppression of PLK1 by miR-509-3-5p is a component of CIS/ADR-induced DDR pathway. Flow cytometry and immunofluorescence labeling showed that over-expression of miR-509-3-5p in A549 induced G2/M arrest and aberrant mitosis characterized by abnormal bipolar mitotic spindles, condensed chromosomes, lagging DNA and chromosome bridges. In addition, over-expression of miR-509-3-5p markedly blocked A549 cell proliferation and sensitized the cells to CIS and ADR treatment. Taken together, miR-509-3-5p is a feasible suppressor for cancer by targeting PLK1. Our data may provide aid in potential design of combined chemotherapy and in our better understanding of the roles of microRNAs in response to DNA damage.

A Type of Low-Latency Data Gathering Method with Multi-Sink for Sensor Networks.

To balance energy consumption and reduce latency on data transmission in Wireless Sensor Networks (WSNs), a type of low-latency data gathering method with multi-Sink (LDGM for short) is proposed in this paper. The network is divided into several virtual regions consisting of three or less data gathering units and the leader of each region is selected according to its residual energy as well as distance to all of the other nodes. Only the leaders in each region need to communicate with the mobile Sinks which have effectively reduced energy consumption and the end-to-end delay. Moreover, with the help of the sleep scheduling and the sensing radius adjustment strategies, redundancy in network coverage could also be effectively reduced. Simulation results show that LDGM is energy efficient in comparison with MST as well as MWST and its time efficiency on data collection is higher than one Sink based data gathering methods.

E2F1 regulates p53R2 gene expression in p53-deficient cells.

The p53R2 gene encoding a small subunit of the ribonucleotide reductase has been identified as a p53-inducible gene. Although this gene is discovered as a target for p53 family proteins, the mechanism underlying p53R2 induction by DNA damage in p53-defiencient cells remains to be elucidated. In this study, we demonstrate that transcription factor E2F1 regulates the p53R2 gene expression in p53-deficient cells. We found that p53R2 was a target for E2F1 in DNA damage response (DDR), because ectopic expression of E2F1 in HCT116-p53(-/-) cells resulted in the increase of p53R2 mRNA and protein expression, and silencing E2F1 diminished its basic expression. Combination of luciferase reporter assay with overexpression or knockdown of E2F1 revealed that E2F1 directly activates the p53R2 gene. Chromatin immunoprecipitation (ChIP) assay showed E2F1 directly bound to the site (TTTGGCGG) at position -684 to -677 of the promoter under E2F1 overexpression or adriamycin (ADR) exposure. Moreover, silencing p53R2 could enhance apoptotic cell death in both HCT116-p53(-/-) and HCT116-p53(+/+) compared to ADR exposure, indicating that p53R2 may protect cancer cell from ADR-induced apoptosis. Together, we have identified a new role of E2F1 in the regulation of p53R2 expression in DDR, and silencing p53R2 may sensitize cancer cells to ADR-induced apoptosis. Our data support the notion that p53R2 is a potential target for cancer therapy. The involvement of E2F1-dependent p53R2 activation in DDR will provide further insight into the induction of p53R2 in p53-deficient cells. These data also give us a deeper understanding of E2F1 role in DDR.

E2F1-regulated DROSHA promotes miR-630 biosynthesis in cisplatin-exposed cancer cells.

DNA damage may regulate microRNA (miRNA) biosynthesis at the levels of miRNA transcription, processing and maturation. Although involvement of E2F1 in the regulation of miRNA gene activation in response to DNA damage has been documented, little is known about the role of E2F1 in miRNA processing. In this study we demonstrate that E2F1 enhances miR-630 biosynthesis under cisplatin (CIS) exposure through promoting DROSHA-mediated pri-miR-630 processing. Northern blot and RT-qPCR revealed that CIS exposure caused not only an increase in pri-miR-630 but also much more increase in pre-miR-630 and mature miR-630. The increases in pri-miR-630 and pre-miR-630 expression in unmatched proportion indicated that primary transcript processing was involved in CIS-stimulated miR-630 biosynthesis. Furthermore, combination of reporter enzyme assay with mutation and over-expression of E2F1 showed that induction of DROSHA promoted miR-630 expression, in which CIS-induced E2F1 activated DROSHA gene expression by recognizing and binding two E2F1 sites at the positions -214/-207 and -167/-160 of the DROSHA promoter. The increased binding of E2F1 to the DROSHA promoter in CIS-exposed cells was further evidenced by chromatin immunoprecipitation assay. Together, E2F1-regulated DROSHA promotes pri-miR-630 processing, thereby, contributes to CIS-stimulated miR-630 expression. The involvement of E2F1-dependent DROSHA activation in pri-miRNA processing under DNA damage stress will provide further insight into the regulation of miRNA biosynthesis. These data also give us a deeper understanding of E2F1 role in response to DNA damage.

p53 Suppresses E2F1-dependent PLK1 expression upon DNA damage by forming p53-E2F1-DNA complex.

E2F1 is implicated in transcriptional activation of polo-like kinase-1 (PLK1), but yet the mechanism is not fully understood. PLK1 suppression plays an important checkpoint role in response to DNA damage. Suppression of the PLK1 gene by binding of p53 to upstream p53RE2 element in the promoter has been recently revealed. Here we report another mechanism, in which p53 interacts with E2F1 to form p53-E2F1-DNA complex repressing E2F1-dependent PLK1 expression. PLK1 was downregulated in cisplatin exposed HCT116p53(+/+) but not HCT116p53(-/-) cells, indicating p53-suppressed PLK1 upon DNA damage. Co-transfection and reporter enzyme assays revealed that p53 suppressed but E2F1 promoted PLK1 gene activation. 5'-Deletion and substitution mutations showed multiple positive cis-elements residing in the PLK1 promoter, of which at least two E2F1 sites at positions -75/-68 and -40/-32 were required for the full activity of the promoter. Combination of 5'-deletion and substitution mutations with over-expression of p53 showed that suppression of the PLK1 gene by p53 was E2F1-dependent: mutation of the E2F1 site at position -75/-68 partially abrogated suppression activity of p53; mutation of E2F1 site at position -40/-32 released from p53 suppression of PLK1 gene completely. Co-immunoprecipitation and electrophoretic mobility shift assay showed that DNA damage promoted p53-E2F1 interaction, thereby creating a p53-E2F1 complex assembly on the PLK1 promoter in vitro. The in vivo formation of p53-E2F1-PLK1 promoter complex upon DNA damage was further evidenced by chromatin immunoprecipitation (ChIP) and re-ChIP. In addition, we showed that suppression of PLK1 by p53 promoted apoptosis. Our data suggest that p53 may interact with E2F1 to form p53-E2F1-DNA complex suppressing E2F1-dependent PLK1 expression. The model of p53 action on E2F1-activated PLK1 gene may explain at least partly how p53 as a suppressor regulates the downstream effects of E2F1 in cellular stresses including DNA damage stress.

E2F1-mediated DNA damage is implicated in 8-Cl-adenosine-induced chromosome missegregation and apoptosis in human lung cancer H1299 cells.

Although E2F1-mediated DNA double-stranded breaks (DSBs) and tetraploid have been extensively studied, the role of E2F1 in mitotic catastrophe is still unknown. We have previously shown that 8-chloro-adenosine (8-Cl-Ado) induces DNA DSBs and aberrant mitosis in human lung cancer cells, followed by delayed apoptosis. Here, we demonstrate that E2F1-mediated DNA damage is implicated in 8-Cl-Ado-induced chromosome missegregation and apoptosis in lung cancer H1299 cells. We showed that E2F1 was accumulated upon 8-Cl-Ado-induced DNA DSBs. Induction of E2F1 by 8-Cl-Ado caused DNA damage in cycling cells including M cells. In contrast, silencing of E2F1 expression decreased 8-Cl-Ado-induced DNA DSBs, particularly eliminated E2F1-mediated mitotic DNA damage. Over-expression of E2F1 and/or 8-Cl-Ado exposure resulted in aberrant mitotic spindles and chromosome segregation errors. Furthermore, over-expression of E2F1 expression enhanced 8-Cl-Ado-induced apoptosis. Together, our data indicate that E2F1-mediated DNA damage, in particular mitotic DNA damage, is an important fraction of 8-Cl-Ado-induced DNA damage, which is implicated in 8-Cl-Ado-induced mitotic catastrophe and delayed apoptosis. Induction of E2F1 by 8-Cl-Ado may contribute at least partly to the drug-inhibited proliferation of cancer cells.

E2F1 enhances 8-chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells.

The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in response to DNA damage is less clear. 8-Chloro-adenosine (8-Cl-Ado), a nucleoside analog, can inhibit proliferation in a variety of human tumor cells. However, it is still elusive how the agent acts on tumors. Here we show that A549 and H1299 cells formed DNA double-strand breaks after 8-Cl-Ado exposure, accompanied by E2F1 upregulation at protein level. Overexpressed wild-type (E2F1-wt) colocalized with double-strand break marker γ-H2AX and promoted G2/M arrest in 8-Cl-Ado-exposed A549 and H1299, while expressed S31A mutant of E2F1 (E2F1-mu) significantly reduced ability to accumulate at sites of DNA damage and G2/M arrest, suggesting that E2F1 is required for activating G2/M checkpoint pathway upon DNA damage. Transfection of either E2F1-wt or E2F1-mu plasmid promoted apoptosis in 8-Cl-Ado-exposed cells, indicating that 8-Cl-Ado may induce apoptosis in E2F1-dependent and E2F1-independent ways. These findings demonstrate that E2F1 plays a crucial role in 8-Cl-Ado-induced G2/M arrest but is dispensable for 8-Cl-Ado-induced apoptosis. These data also suggest that the mechanism of 8-Cl-Ado action is complicated.

Can a single-port robot be safely used for robotic total gastrectomy for advanced gastric cancer? First experience using the da Vinci SP platform.

Background: Many studies have shown the operative feasibility and safety of robotic gastrectomy. Surgeons are pursuing single-port (SP) surgery to leverage the advantages of minimally invasive gastrectomy. The purpose of this study was to describe technical considerations and short-term outcomes from the first reported SP robotic total gastrectomy (RTG) using the da Vinci SP platform. Methods: A 75-year-old patient with a body-mass index of 19.8 kg/m2 and clinical stage III cancer (cT3N+M0) underwent SP RTG on 22 January 2022 at the Department of General Surgery, the Chinese PLA General Hospital. All procedures were performed successfully using the da Vinci SP robotic platform. Results: The SP RTG was successfully performed with D2 lymphadenectomy including No. 10 lymph-nodes dissection and extracorporeal Roux-en-Y anastomosis. Except for subcutaneous emphysema, no severe adverse events occurred during the operation. According to a visual analogue scale (VAS), the subjective feeling of post-operative pain was given a VAS score of 3 of 10 on Post-Operative Day 1 (POD 1), 1 of 10 on POD 3, and 1 of 10 on POD 7. We removed the gastric tube on POD 2 and advised sipping water, a liquid diet, and a soft diet on PODs 2, 4, and 6, respectively. The patient was discharged without any complications on POD 8. Conclusion: RTG is technically feasible and safe using the da Vinci SP robotic platform. To our knowledge, this is the first study using the da Vinci SP platform in RTG for advanced gastric cancer in elderly patients. To verify its superior operative outcomes, further clinical trials are needed.

Obacunone protects retinal pigment epithelium cells from ultra-violet radiation-induced oxidative injury.

Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. In vivo, intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.

p14ARF interacts with E2F factors to form p14ARF-E2F/partner-DNA complexes repressing E2F-dependent transcription.

Primarily, E2F factors such as E2F1, -2, and -3 stimulate cell-cycle progression, while ARF tumor suppressor mediates growth suppression. The ARF gene can be induced by oncogenic signal through activating E2F-dependent transcription. In turn, ARF may target E2F for its degradation via a p53-dependent mechanism. However, it remains unclear how the cell keeps the balance between the functional opposites of E2F and ARF. In this study, we demonstrate that p14ARF interacts with E2F1-3 factors to directly repress their transcriptional activities through forming p14ARF-E2F/partner-DNA super complexes, regardless of E2F protein degradation. The inhibition of E2F transcriptional activities by p14ARF in this manner occurs commonly in a variety of cell types, including p53-deficient and p53-wild type cells. Thus, E2F-mediated activation of the ARF gene and ARF-mediated functional inhibition of E2F compose a feedback loop, by which the two opposites act in concert to regulate cell proliferation and apoptosis, depending on the cellular context and the environment.

Calcium signal-initiated early activation of NF-kappaB in neurons is a neuroprotective event in response to kainic acid-induced excitotoxicity.

We demonstrate that activation of nuclear factor kappaB (NF-kappaB) in neurons is neuroprotective in response to kainic acid (KA)-induced excitotoxicity. Combination of Western blotting, immunocytochemistry, and electrophoresis mobility shift assay showed that KA exposure induced a fast but transient nuclear translocation of the NF-kappaB p65 subunit and increased DNA-binding activity of NF-kappaB in primary cultured cortical neurons. The transient NF-kappaB activity was associated with upregulation of antiapoptotic Bcl-xL and XIAP gene products revealed by real-time PCR. Knockdown of p65 decreased neuronal viability and antiapoptotic gene expression. In addition, we showed that KA-stimulated DNA-binding activity of NF-kappaB was associated with reactive oxygen species and calcium signals, using AMPA/KA receptor antagonist, calcium chelator, and antioxidant. These results suggest that the fast and transient activation of NF-kappaB initiated by calcium signals is one of the important proximal events in response to KA-induced excitotoxicity, which has neuroprotective effect against KA-induced apoptosis.

A Systematic Analysis of Dysregulated Long Non-Coding RNAs/microRNAs/mRNAs in Lung Squamous Cell Carcinoma.

BACKGROUND: Lung squamous cell carcinoma (LUSC) accounts up for approximately 30% of all lung cancers with a high mortality. The study was aimed at finding genes critical in the diagnosis and prognosis of LUSC. MATERIALS AND METHODS: The differentially expressed (DE) genes (DEGs) and DE lncRNAs (DELs) from 501 LUSC and 49 normal lung tissues, and DE miRNAs (DEMs) from 478 LUSC and 45 normal lung tissues were respectively obtained via the TCGA database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and co-expression network analyses were performed. Survival analysis and receiver operating characteristic curve of hub mRNAs were also analyzed. Competitive endogenous RNA networks of lncRNAs, miRNAs and mRNAs were constructed. RESULTS: A total of 5747 DEGs, 378 DEMs and 3141 DELs in LUSC were identified in LUSC. The DEGs including AUARK, CDK1, KIF11 and EXO1 were proven to be significant metastatic indicators in LUSC, and 2 DEGs were significantly associated with the survival in LUSC patients. Some genes might have connections with many other gene nodes through a co-expression network. Four lncRNAs, 2 mRNAs and 2 miRNAs were identified as the candidates for the competitive miRNA-mRNA-lncRNA network and might serve as prognostic markers in LUSC. CONCLUSIONS: We identified the differentially expressed lncRNAs, miRNAs and mRNAs in LUSC, providing further insights into the molecular mechanism of LUSC tumorigenesis and the potential prognostic biomarkers or therapeutic targets for LUSC.

MiR-509-3-5p-NONHSAT112228.2 Axis Regulates p21 and Suppresses Proliferation and Migration of Lung Cancer Cells.

BACKGROUND: Although the involvement of individual microRNA and lncRNA in the regulation of p21 expression has largely been evidenced, less is known about the roles of functional interactions between miRNAs and lncRNAs in p21 expression. Our previous work demonstrated that miR-509- 3-5p could block cancer cell growth. METHODS: To gain an insight into the role of miR-509-3-5p in the regulation of p21 expression, we performed in silico prediction and showed that miR-509-3-5p might target the NONHSAT112228.2, a sense-overlapping lncRNA transcribed by a non-code gene overlapping with p21 gene. Mutation and luciferase report analysis suggested that miR-509-3-5p could target NONHSAT112228.2, thereby blocking its expression. Consistently, NONHSAT112228.2 expression was inversely correlated with both miR-509-3-5p and p21 expression in cancer cells. Ectopic expression of miR-509-3-5p and knockdown of NONHSAT112228.2 both promoted proliferation and migration of cancer cells. RESULTS: Interestingly, high-expression of NONHSAT112228.2 accompanied by low-expression of p21 was observed in lung cancer tissues and associated with lower overall survival. CONCLUSION: Taken together, our study found a new regulatory pathway of p21, in which MiR-509-3-5p functionally interacts with NONHSAT112228.2 to release p21 expression. MiR-509-3-5p- NONHSAT112228.2 regulatory axis can inhibit the proliferation and migration of lung cancer cells.