Genetic lineage tracing in skin reveals predominant expression of HEY2 in dermal papilla during telogen and that HEY2+ cells contribute to the regeneration of dermal cells during wound healing.

Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear what the source of progenitor cells is for dermal cell regeneration during wound healing, and whether DP cells are involved in this process. We analyzed the gene expression profile of various skin cell populations using existing datasets and found that the Hey2 gene was predominantly expressed in DP cells. We introduced Hey2-CreERT2 knockin mice and crossed them with Rosa26-ZsGreen reporter mice. After induction in the double transgenic mice by administration of tamoxifen, the reporter ZsGreen was found to be predominantly expressed in DP cells both at anagen and telogen phases, and broadly expressed in some other dermal cells at anagen. We also created a wound after tamoxifen induction, and found there were abundant ZsGreen+ cells in the regenerated dermis. We conclude that the HEY2+ DP cells and dermal cells exhibit some stemness properties and can contribute to the dermal cell regeneration during wound healing.

Sensitive Quantitative In Vivo Assay for Evaluating the Effects of Biomolecules on Hair Growth and Coloring Using Direct Microinjections into Mouse Whisker Follicles.

Many people suffer from hair loss and abnormal skin pigmentation, highlighting the need for simple assays to support drug discovery research. Current assays have various limitations, such as being in vitro only, not sensitive enough, or unquantifiable. We took advantage of the bilateral symmetry and large size of mouse whisker follicles to develop a novel in vivo assay called "whisker follicle microinjection assay". In this assay, we plucked mouse whiskers and then injected molecules directly into one side of the whisker follicles using microneedles that were a similar size to the whiskers, and we injected solvent on the other side as a control. Once the whiskers grew out again, we quantitatively measured their length and color intensity to evaluate the effects of the molecules on hair growth and coloring. Several chemicals and proteins were used to test this assay. The chemicals minoxidil and ruxolitinib, as well as the protein RSPO1, promoted hair growth. The effect of the clinical drug minoxidil could be detected at a concentration as low as 0.001%. The chemical deoxyarbutin inhibited melanin production. The protein Nbl1 was identified as a novel hair-growth inhibitor. In conclusion, we successfully established a sensitive and quantitative in vivo assay to evaluate the effects of chemicals and proteins on hair growth and coloring and identified a novel regulator by using this assay. This whisker follicle microinjection assay will be useful when investigating protein functions and when developing drugs to treat hair loss and abnormal skin pigmentation.

Case Report: Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy for gastric cancer in a patient with situs inversus totalis: with video.

Because of its significant advantage of fast postoperative recovery, natural orifice specimen extraction surgery (NOSES) has attracted increasing attention worldwide. However, the NOSES in gastric cancer (GC) treatment still needs more clinical practice, especially for the rare anatomical anomaly. Situs inversus totalis (SIT) is a rare autosomal recessive anatomical anomaly with an incidence ranging between 1/8,000 and 1/25,000 births. We present a video of transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy performed in a 59-year-old woman known to have SIT. Preoperative investigations revealed that the patient had early GC at the antrum. A gastroscopy report from the local hospital showed signet-ring cell carcinoma. The preoperative computed tomography scan revealed irregular thickening of the gastric wall at the junction of the greater curvature and antrum without metastasis to the lymph nodes. In total, laparoscopic D2 distal gastrectomy was performed with transvaginal specimen extraction. Billroth II with Braun anastomosis was performed for reconstruction. The length of the operation was 240 min without intraoperative complications and with minimal blood loss of 50 ml. The patient was uneventfully discharged on postoperative Day 7. The final pathology confirmed signet-ring cell carcinoma confined to the mucosal muscle without metastasis in 16 lymph nodes. Transvaginal specimen extraction following totally laparoscopic D2 distal gastrectomy can be safely performed in patients with SIT and has similar surgical outcomes to usual laparoscopic gastrectomy.

SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis.

Purpose: Silent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD). Materials and methods: Human immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism. Results: SGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD. Conclusion: The SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC.

A Cre knockin mouse reveals specific expression of Agouti gene in mesenchymal lineage cells in multiple organs and provides a unique tool for conditional gene targeting.

The mouse Agouti gene encodes a paracrine signaling factor which promotes melanocytes to produce yellow instead of black pigment. It has been reported that Agouti mRNA is confined to the dermal papilla after birth in various mammalian species. In this study, we created and characterized a knockin mouse strain in which Cre recombinase was expressed in-frame with endogenous Agouti coding sequence. The Agouti-Cre mice were bred with reporter mice (Rosa26-tdTomato or Rosa26-ZsGreen) to trace the lineage of Agouti-expressing cells during development. In skin, the reporter was detected in some dermal fibroblasts at the embryonic stage and in all dermal fibroblasts postnatally. It was also expressed in all mesenchymal lineage cells in other organs/tissues, including eyes, tongue, muscle, intestine, adipose, prostate and testis. Interestingly, the reporter expression was excluded from epithelial cells in the above organs/tissues. In brain, the reporter was observed in the outermost meningeal fibroblasts. Our work helps to illustrate the Agouti expression pattern during development and provides a valuable mouse strain for conditional gene targeting in mesenchymal lineage cells in multiple organs.

SCD1 Sustains Homeostasis of Bulge Niche via Maintaining Hemidesmosomes in Basal Keratinocytes.

Niche for stem cells profoundly influences their maintenance and fate during tissue homeostasis and pathological disorders; however, the underlying mechanisms and tissue-specific features remain poorly understood. Here, it is reported that fatty acid desaturation catabolized by stearoyl-coenzyme A desaturase 1 (SCD1) regulates hair follicle stem cells (HFSCs) and hair growth by maintaining the bulge, niche for HFSCs. Scd1 deletion in mice results in abnormal hair growth, an effect exerted directly on keratin K14+ keratinocytes rather than on HFSCs. Mechanistically, Scd1 deficiency impairs the level of integrin α6ß4 complex and thus the assembly of hemidesmosomes (HDs). The disruption of HDs allows the aberrant activation of focal adhesion kinase and PI3K in K14+ keratinocytes and subsequently their differentiation and proliferation. The overgrowth of basal keratinocytes results in downward extension of the outer root sheath and interruption of bulge formation. Then, inhibition of PI3K signaling in Scd1-/- mice normalizes the bulge, HFSCs, and hair growth. Additionally, supplementation of oleic acid to Scd1-/- mice reestablishes HDs and the homeostasis of bulge niche, and restores hair growth. Thus, SCD1 is critical in regulating hair growth through stabilizing HDs in basal keratinocytes and thus sustaining bulge for HFSC residence and periodic activity.

Expression dynamics of lymphoid enhancer-binding factor 1 in terminal Schwann cells, dermal papilla, and interfollicular epidermis.

BACKGROUND: Transcription factor lymphoid enhancer-binding factor 1 (LEF1) is a downstream mediator of the Wnt/ß-catenin signaling pathway. It is expressed in dermal papilla and surrounding cells in the hair follicle, promoting cell proliferation, and differentiation. RESULTS: Here, we report that LEF1 is also expressed all through the hair cycle in the terminal Schwann cells (TSCs), a component of the lanceolate complex located at the isthmus. The timing of LEF1 appearance at the isthmus coincides with that of hair follicle innervation. LEF1 is not found at the isthmus in the aberrant hair follicles in nude mice. Instead, LEF1 in TSCs is found in the de novo hair follicles reconstituted on nude mice by stem cells chamber graft assay. Cutaneous denervation experiment demonstrates that the LEF1 expression in TSCs is independent of nerve endings. At last, LEF1 expression in the interfollicular epidermis during the early stage of skin development is significantly suppressed in transgenic mice with T-cell factor 3 (TCF3) overexpression. CONCLUSION: We reveal the expression dynamics of LEF1 in skin during development and hair cycle. LEF1 expression in TSCs indicates that the LEF1/Wnt signal might help to establish a niche at the isthmus region for the lanceolate complex, the bulge stem cells and other neighboring cells.

An integrated, cross-regulation pathway model involving activating/adaptive and feed-forward/feed-back loops for directed oscillatory cAMP signal-relay/response during the development of Dictyostelium.

Self-organized and excitable signaling activities play important roles in a wide range of cellular functions in eukaryotic and prokaryotic cells. Cells require signaling networks to communicate amongst themselves, but also for response to environmental cues. Such signals involve complex spatial and temporal loops that may propagate as oscillations or waves. When Dictyostelium become starved for nutrients, cells within a localized space begin to secrete cAMP. Starved cells also become chemotactic to cAMP. cAMP signals propagate as outwardly moving waves that oscillate at ∼6 min intervals, which creates a focused territorial region for centralized cell aggregation. Proximal cells move inwardly toward the cAMP source and relay cAMP outwardly to recruit additional cells. To ensure directed inward movement and outward cAMP relay, cells go through adapted and de-adapted states for both cAMP synthesis/degradation and for directional cell movement. Although many immediate components that regulate cAMP signaling (including receptors, G proteins, an adenylyl cyclase, phosphodiesterases, and protein kinases) are known, others are only inferred. Here, using biochemical experiments coupled with gene inactivation studies, we model an integrated large, multi-component kinetic pathway involving activation, inactivation (adaptation), re-activation (re-sensitization), feed-forward, and feed-back controls to generate developmental cAMP oscillations.

Triazine-Based Covalent DNA-Encoded Libraries for Discovery of Covalent Inhibitors of Target Proteins.

Since ibrutinib was approved by the FDA as an effective monotherapy for chronic lymphocytic leukemia (CLL) and multilymphoma, more and more FDA-approved covalent drugs are coming back into the market. On this occasion, the resurgence of interest in covalent drugs calls for more hit discovery techniques. However, the limited numbers of covalent libraries prevent the development of this area. Herein, we report the design of covalent DNA-encoded library (DEL) and its selection method for the discovery of covalent inhibitors for target proteins. These triazine-based covalent DELs yielded potent compounds after covalent selection against target proteins, including Bruton's Tyrosine Kinase (BTK), Janus kinase 3 (JAK3), and peptidyl-prolyl cis/trans isomerase NIMA-interacting-1 (Pin1).

Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed and treated in advanced tumor stages with poor prognosis. More effective screening programs and novel therapeutic means are urgently needed. Recent studies have regarded tight junction protein claudin 18.2 (CLDN18.2) as a candidate target for cancer treatment, and zolbetuximab (formerly known as IMAB362) has been developed against CLDN18.2. However, there are few data reported thus far related to the clinicopathological characteristics of CLDN18.2 expression for PDAC. AIM: To investigate the expression of CLDN18.2 in PDAC patients and subsequently propose a new target for the treatment of PDAC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, and European Genome-phenome Archive databases were first employed to analyze the CLDN18 gene expression in normal pancreatic tissue compared to that in pancreatic cancer tissue. Second, we analyzed the expression of CLDN18.2 in 93 primary PDACs, 86 para-cancer tissues, and 13 normal pancreatic tissues by immunohistochemistry. Immunostained tissues were assessed applying the histoscore. subsequently, they fell into two groups according to the expression state of CLDN18.2. Furthermore, the correlations between CLDN18.2 expression and diverse clinicopathological characteristics, including survival, were investigated. RESULTS: The gene expression of CLDN18 was statistically higher (P < 0.01) in pancreatic tumors than in normal tissues. However, there was no significant correlation between CLDN18 expression and survival in pancreatic cancer patients. CLDN18.2 was expressed in 88 (94.6%) of the reported PDACs. Among these tumors, 50 (56.8%) cases showed strong immunostaining. The para-cancer tissues were positive in 81 (94.2%) cases, among which 32 (39.5%) of cases were characterized for strong staining intensities. Normal pancreatic tissue was identified solely via weak immunostaining. Finally, CLDN18.2 expression significantly correlated with lymph node metastasis, distant metastasis, nerve invasion, stage, and survival of PDAC patients, while there was no correlation between CLDN18.2 expression and localization, tumor size, patient age and sex, nor any other clinicopathological characteristic. CONCLUSION: CLDN18.2 expression is frequently increased in PDAC patients. Thus, it may act as a potential therapeutic target for zolbetuximab in PDAC.

Large-scale isolation of functional dermal papilla cells using novel surface marker LEPTIN Receptor.

Dermal papilla (DP) cells regulate hair follicle epithelial cells and melanocytes by secreting functional factors, playing a key role in hair follicle morphogenesis and hair growth. DP cells can reconstitute new hair follicles and induce hair regeneration, providing a potential therapeutic strategy for treating hair loss. However, current methods for isolating DP cells are either inefficient (physical microdissection) or only applied to genetically labeled mice. We systematically screened for the surface proteins specifically expressed in skin DP using mRNA expression databases. We identified two antibodies against receptors LEPTIN Receptor (LEPR ) and Scavenger Receptor Class A Member 5 (SCARA5) which could specifically label and isolate DP cells by flow cytometry from mice back skin at the growth phase. The sorted LEPR+ cells maintained the DP characteristics after culturing in vitro, expressing DP marker alkaline phosphatase and functional factors including RSPO1/2 and EDN3, the three major DP secretory factors that regulate hair follicle epithelial cells and melanocytes. Furthermore, the low-passage LEPR+ DP cells could reconstitute hair follicles on nude mice using chamber graft assay when combined with epithelial stem cells. The method of isolating functional DP cells we established here lays a solid foundation for developing DP cell-based therapy.

CircRNA-ABCB10 promotes gastric cancer progression by sponging miR-1915-3p to upregulate RaC1.

BACKGROUND: Gastric cancer (GC) is a common malignant tumor of the digestive system. Increasing reports have demonstrated the crucial roles of circRNAs in tumorigenesis and progression of GC. METHODS: The relative expression of circ-ABCB10 in GC tissues and cell lines was detected by qRT-PCR. A series of in vitro assays and a xenograft model in vivo were applied to explore the function of circ-ABCB10 in GC cells. RESULTS: Circ-ABCB10 expression was upregulated in GC tissues and cell lines and positively correlated with poor survival of GC patients. Circ-ABCB10 downregulation decreased cell viability, inhibited cell growth, invasion, and migration, while promoted cell apoptosis of GC cell lines SGC-7901 and MKN-48. Circ-ABCB10 could upregulate Rac1 expression by directly sponging miR-1915-3p. Rescue experiments revealed that miR-1915-3p inhibitor obviously reversed the inhibitory effect of si-circ-ABCB10, and Rac1 overexpression obviously reversed the inhibitory effect of miR-1915-3p mimics on cell growth, invasion, migration, apoptosis, and cell cycle progression. Moreover, si-circ-ABCB10 effectively inhibited tumor growth in a xenograft model. CONCLUSIONS: Our study revealed that circ-ABCB10 promoted GC progression via targeting the miR-1915-3p/Rac1 axis, and circ-ABCB10 might be a potential target for GC diagnosis and treatment.

A Nomogram Model Involving Preoperative Fibrinogen and Prognostic Nutritional Index Score for Predicting Postoperative Outcome in Patients with Gastric Cancer.

BACKGROUND: Inflammation and nutrition play vital roles in the development of gastric cancer (GC). We combined the preoperative fibrinogen with prognostic nutritional index (PNI) to create a novel scoring system named as the fibrinogen and prognostic nutritional index (FPNI) score and establish a more effective model. PATIENTS AND METHODS: A total of 689 patients with gastric adenocarcinoma who underwent gastrectomy from January 2012 to December 2016 were reviewed. We measured correlations between FPNI score and clinicopathological variables and overall survival (OS). A nomogram predicting OS was constructed. Its predictive performance was verified using the concordance index, calibration curves, receiver operating characteristic curves, decision curve analysis and time-dependent receiver operating characteristic analysis. RESULTS: We observed that the FPNI score was an independent predictor of OS in patients with gastric cancer (P < 0.05). A high FPNI score was significantly related to older age at surgery, tumor size ≥4.6 cm, high ASA score, advanced TNM stage and poor outcome (both P < 0.05). And the FPNI score remained an independent indicator at various TNM stages (P < 0.05). Ultimately, the nomogram based on FPNI score, age, tumor size, histological grade and TNM stage showed a better predictive ability than TNM alone. CONCLUSION: The preoperative FPNI score is a novel, simple, and effective predictor of OS in patients with GC. Furthermore, the nomogram involving FPNI score will help clinicians to optimize individualized treatment plans.

A nomogram combining plasma fibrinogen and systemic immune­inflammation index predicts survival in patients with resectable gastric cancer.

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.

Targeting COX-2 potently inhibits proliferation of cancer cells in vivo but not in vitro in cutaneous squamous cell carcinoma.

BACKGROUND: Cyclooxygenase 2 (COX-2) is an inducible enzyme which promotes tumorigenesis in many types of cancers. Genetic knockout of COX-2 significantly suppresses the tumorigenesis of skin squamous cell carcinoma (SCC). However, COX-2 inhibitor treatment only showed mild to moderate inhibition on SCC in previous reports. The aim of this study is to solve this contradiction and to re-evaluate the therapeutic potential of targeting COX-2 in SCC. METHODS: COX-2 was knocked down by shRNA in two different SCC cell lines, A431 and SCC-13. The cells proliferation and migration capacity were evaluated by cell growth curves and monolayer scratch assay, respectively. Cancer cells with COX-2 knockdown were also xenografted into Balb/c nude mice and tumor growth curves were recorded over time. In addition, we changed the drug administration route and intraperitoneally injected COX-2 inhibitor celecoxib into mice to evaluate its anti-cancer activity. RESULTS: Knockdown of COX-2 exhibited mild or even no effect on cell proliferation and migration in two different SCC cell lines in vitro. However, when cancer cells were xenografted into nude mice, knockdown of COX-2 significantly suppressed proliferation of cancer cells in tumors. At last, intraperitoneal injection instead of oral administration of COX-2 inhibitor celecoxib potently suppressed tumor growth. CONCLUSIONS: Our results indicate that COX-2 might impact on the interaction between cancer cells and surrounding microenvironments rather than on cancer cells directly, and demonstrate that targeting COX-2 is a very promising therapeutic approach for SCC treatment.

Neuritin-overexpressing transgenic mice demonstrate enhanced neuroregeneration capacity and improved spatial learning and memory recovery after ischemia-reperfusion injury.

Acute ischemia-reperfusion (IR)-induced brain injury is further exacerbated by a series of slower secondary pathogenic events, including delayed apoptosis due to neurotrophic factor deficiency. Neuritin, a neurotrophic factor regulating nervous system development and plasticity, is a potential therapeutic target for treatment of IR injury. In this study, Neuritin-overexpressing transgenic (Tg) mice were produced by pronuclear injection and offspring with high overexpression used to generate a line with stable inheritance for testing the neuroprotective capacity of Neuritin against transient global ischemia (TGI). Compared to wild-type mice, transgenic mice demonstrated reduced degradation of the DNA repair factor poly [ADP-ribose] polymerase 1 (PARP 1) in the hippocampus, indicating decreased hippocampal apoptosis rate, and a greater number of surviving hippocampal neurons during the first week post-TGI. In addition, Tg mice showed increased expression of the regeneration markers NF-200, synaptophysin, and GAP-43, and improved recovery of spatial learning and memory. Our findings exhibited that the window of opportunity of neural recovery in Neuritin transgenic mice group had a tendency to move ahead after TGI, which indicated that Neuritin can be used as a potential new therapeutic strategy for improving the outcome of cerebral ischemia injury.

Spatial association of SEMA3C with nerve endings/terminal Schwann cells in hair follicle isthmus region.

Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular-junction-like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here, we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle.

Calcitonin gene-related peptide receptor Calcrl is enriched in hair follicles stem cells and differentially expressed in interfollicular epidermis in murine skin.

Calcitonin gene-related peptide (CGRP) and adrenomedullin are structurally similar neuropeptides acting as potent vasodilators of blood pressure and mediator of inflammation in skin. Revealing the expression pattern of their common receptor-Calcitonin gene-related peptide receptor (Calcrl) in their targeted cells is important to explain the functions of CGRP and adrenomedullin in skin. Our immunostaining results showed that Calcrl is enriched in hair follicles bulge stem cells and differentially expressed in basal stem cells of interfollicular epidermis. In addition, Calcrl expression in interfollicular epidermis is dependent on presence of nerve fibers. Long-term ablation of the murine cutaneous nerve leads to loss of Calcrl expression in interfollicular epidermis but not in hair follicle bulge stem cells. Our results demonstrate a tight interaction between neuronal components and epidermis, and indicates potential roles of Calcrl in epidermal stem cells.

MicroRNA-223-5p targets long non-coding RNA TP73 antisense RNA1 to promote the invasion of gastric cancer.

Long non-coding RNA (lncRNA) TP73 antisense RNA 1 (TP73-AS1) has been characterized as an oncogenic lncRNA in GC. However, by analyzing The Cancer Genome Atlas (TCGA) dataset we observed the downregulation of TP73-AS1 in GC. In addition, TP73-AS1 is predicted to interact with microRNA-223-5p (miR-223-5p), which is also a critical player in cancer biology. This study was therefore carried out to investigate the roles of miR-223-5p and TP73-AS1 in gastric cancer (GC) and to explore the interactions between them. In this study, 68 GC patients were included as research subjects. Expression of miR-223-5p and TP73-AS1 was analyzed by RT-qPCR. Dual-luciferase assay and overexpression experiments were used to analyze gene interactions. Transwell assays were used to analyze cell invasion and migration. We found that miR-223-5p was upregulated and TP73-AS1 was downregulated in GC and they were inversely correlated. Altered miR-223-5p and TP73-AS1 expression predicted poor disease-specific survival. Dual-luciferase assay showed that miR-223-5p may bind TP73-AS1 and overexpression experiments showed that miR-223-5p overexpression downregulated TP73-AS1 in gastric cancer cells. Cell invasion and migration assays showed that miR-223-5p could promote the invasion and migration of gastric cancer cells, while TP73-AS1 could inhibit the invasion and migration of gastric cancer cells. In addition, miR-223-5p attenuated the effects of TP73-AS1 overexpression. Therefore, miR-223-5p may target TP73-AS1 to promote the invasion and migration of gastric cancer patients.