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ObjectivesThis study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population.DesignLarge-scale population-based cohort study based on a prospective cohort.SettingUK Biobank cohort linked to multiple nationwide electronic health records databases.ParticipantsThe cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak.Main outcome measuresMain outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting.ResultsCompared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group.ConclusionsOur study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up.

Previous reports have shown that histone deacetylase inhibitors (HDACi) can alter miRNA expression in a range of cancers. Both the 5p-arm and 3p-arm of mature miRNAs can be expressed from the same precursor and involved in cancer progress. Nevertheless, the detailed mechanism by which vorinostat (SAHA), a HDACi, triggers miR-769-5p/miR-769-3p-mediated suppression of proliferation and induces apoptosis in gastric cancer (GC) cells remains elusive. Here, we showed that the miRNA-seq analysis of GC cells treated with SAHA identified seven differentially expressed miRNAs with both strands of the miRNA duplex. miR-769-5p/miR-769-3p expression was downregulated in GC tissues compared with normal tissues. Functionally, high expression of miR-769-5p/miR-769-3p blocked the malignant abilities of GC cells. Mechanistically, miR-769-5p/miR-769-3p targeted IGF1R and IGF1R overexpression rescued the effects of miR-769-5p/miR-769-3p on GC cells growth and metastasis. Moreover, STAT3 bound to the promoter of miR-769. Furthermore, miR-769-5p/miR-769-3p expression was negatively regulated by the STAT3-IGF1R-HDAC3 complex. Besides, miR-769-5p/miR-769-3p synergized with SAHA to promote GC cells apoptosis. Our studies suggest that miR-769-5p/miR-769-3p acts as a tumor suppressor by the STAT3-IGF1R-HDAC3 complex. Moreover, SAHA triggers miR-769-5p/miR-769-3p-mediated inhibition of proliferation and induces apoptosis in GC cells.

In this paper, a high sensitive fiber-optic Fabry-Perot interferometer sensor based on gold diaphragm for acoustic detection has been proposed and experimentally demonstrated. The extrinsic Fabry-Perot interferometer (EFPI) comprises a 140-nm-thick gold diaphragm and the end-face of a fiber-optic collimator, both of which are enclosed into a structure made of glass tubes. A fiber-optic collimator is first adopted in acoustic sensing to reduce the light loss and improve the sensitivity. The experimental results show that the proposed sensor has a wide flat response range from 400 Hz to 12 kHz, almost covering the primary frequency component of audible sound. The pressure sensitivity and the minimum detectable acoustic pressure level (MDP) are measured to be −175.7 dB re 1rad/ $\mu $ Pa@150Hz and $95.3~\mu $ Pa/Hz1/2@2kHz, respectively. The proposed sensor has advantages of high sensitivity, wide flat response, low cost, and simple fabrication, which shows its potential as a fiber optical microphone with high sensitivity and high acoustic quality in practical applications.

HMGA1 protein is an architectural transcription factor that has been implicated in the progression of multiple malignant tumors. However, the role of HMGA1 in the growth and metastasis of gastric cancer (GC) has not yet been elucidated. Here, we show that HMGA1 is overexpressed in GC cells and the high expression of HMGA1 was correlated with worse survival in GC patients using a bioinformatics assay. Functionally, HMGA1 affected the EdU incorporation, colony formation, migration and invasion of GC cells by exogenously increasing or decreasing the expression of HMGA1. Mechanistically, HMGA1 directly bound to the SUZ12 and CCDC43 promoter and transactivated its expression in GC cells. Inhibition of SUZ12 and CCDC43 attenuated the proliferation, migration and invasiveness of HMGA1-overexpressing GC cells in vitro. Moreover, both HMGA1 and SUZ12/CCDC43 were highly expressed in cancer cells but not in normal gastric tissues, and their expressions were positively correlated. Finally, a tail vein metastatic assay showed that HMGA1 promoted SUZ12/CCDC43-mediated GC cell metastasis in vivo. Our findings suggest that HMGA1 promotes GC growth and metastasis by transactivating SUZ12 and CCDC43 expression, highlighting HMGA1 as a potential prognostic biomarker in the treatment of GC.

HOXA6 gene plays a role of the oncogene in various cancers. Nonetheless, its effect on gastric cancer (GC) occurrence and development is still unclear. We analysed whether HOXA6 interacts with the PBX2 protein using the STRING database. The molecular mechanism by which HOXA6 synergizes with PBX2 in GC metastasis is not fully understood. Here, we found that the expression of HOXA6 was increased in GC tissues and cell lines. The upregulation of HOXA6 was closely associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients based on tissue microarray (TMA) data. Moreover, the overexpression of HOXA6 promoted, whereas siRNA-mediated repression of HOXA6 inhibited, the cell proliferation, migration, and invasion of GC cells. Furthermore, HOXA6 could physically interact with and stabilize PBX2. In addition, HOXA6 and PBX2 expression was positively correlated in GC cells and tissue. HOXA6 and PBX2 suppression in GC cells also led to decreased migration and invasion potential in vitro. In vivo, HOXA6 was shown to cooperate with PBX2 to enhance cell metastasis via orthotopic implantation. These data indicate that HOXA6 promotes cell proliferation, migration, and invasion and that the HOXA6-PBX2 axis may be a useful biomarker for disease progression in GC.

Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman’s correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells.

Previous studies have shown an association between coiled-coil domain-containing (CCDC) genes and different cancers. Our previous studies revealed that CCDC43 is highly expressed in colorectal cancer, but the expression and molecular mechanisms of CCDC43 in gastric cancer (GC) are yet to be determined. Here, we show that CCDC43 is overexpressed in gastric tissues. CCDC43 expression is closely related to tumor differentiation, lymph-node-metastasis, and prognosis of gastric cancer. Overexpression of CCDC43 promotes the proliferation, invasion, and metastasis of GC cells. CCDC43 may upregulate and stabilize ADRM1, resulting in the construction of the ubiquitin-mediated proteasome. In contrast, inhibition of ADRM1 could reverse the function of CCDC43 in GC both in vitro and in vivo. Our data demonstrate that transcription factor YY1 directly binds to CCDC43 and ADRM1 gene promoters, leading to over-expression of CCDC43 and ADRM1. Furthermore, in vitro experiments demonstrate that knock down of CCDC43 or ADRM1 attenuates the YY1-mediated malignant phenotypes. Finally, the association among YY1, CCDC43 and ADRM1 is validated in clinical samples. Our findings suggest that the CCDC43-ADRM1 axis regulated by YY1, promotes proliferation and metastasis of GC, and the axis may be a potential therapeutic target for GC.

Background HOXD9, a Hox family member, is involved in cancer growth and metastasis. But, its regulation mechanism at the molecular level particularly in colorectal cancer (CRC), is mostly unknown. Methods The HOXD9 protein expression levels were analyzed using immunofluorescence, immunohistochemistry (IHC) assays, and western blot. The in vivo and in vitro roles of HOXD9 in CRC were determined using colony formation and EdU incorporation, CCK‐8, wound scratch and transwell invasion assay, and animal models. Results Expression of HOXD9 was higher in CRC than in matched healthy tissues. High expression of HOXD9 has significantly associated with the American Joint Committee on Cancer (AJCC) stages, tumor differentiation, lymph node metastasis, and other serious invasions, and it had a poor prognosis. In vitro, HOXD9 encouraged proliferation, movement and EMT processes in cells of CRC. Also, TGF‐β1 promoted the expression of HOXD9 and this effect was dependent on the dose and downregulation of HOXD9 repressed TGF‐β1 ‐induced EMT. In vivo, HOXD9 promoted the invasive and metastasis of CRC cells via orthotopic implantation. Conclusions The ectopic expression of HOXD9 promoted the invasion metastasis in cells of the colorectal tumor by induction of EMT in vitro and vivo., HOXD9 is overexpressed in CRC and increases tumorigenicity and tumor proliferation. Also, ectopic HOXD9 expression influences EMT and tumor spread both in vivo and in vitro. Therefore, the HOXD9 gene could act as an assuring therapeutic approach for treating patients suffering from CRC.

Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the molecular mechanisms underlying miR-3648 progression and metastasis in gastric cancer (GC) remain unclear. miR-3648 expression is downregulated and its ectopic expression in GC cells significantly suppressed cell proliferation and metastasis. Mechanistic analyses indicated that miR-3648 directly targets FRAT1 or FRAT2 and inhibits FRAT1- or FRAT2-mediated invasion and motility in vitro and in vivo. Moreover, FRAT1 physically interacted with FRAT2. Furthermore, FRAT1 overexpression promoted GC cell invasion, whereas siRNA-mediated repression of FRAT2 in FRAT1-overexpressing GC cells reversed its invasive potential. Besides, miR-3648 inactivated the Wnt/β-catenin signalling pathway by downregulating FRAT1 and FRAT2 in GC. Interestingly, c-Myc, a downstream effector of Wnt/β-catenin signalling, was also downregulated by miR-3648 overexpression. In turn, c-Myc negatively regulated miR-3648 expression by binding to the miR-3648 promoter. In addition, miR-3648 expression levels were negatively correlated with c-Myc, FRAT1, and FRAT2 expression in fresh gastric samples. Our studies suggest that miR-3648 acts as a tumour-suppressive miRNA and that the miR-3648/FRAT1-FRAT2/c-Myc negative feedback loop could be a critical regulator of GC progression.

The coiled-coil domain-containing protein 43 (CCDC43) is essential to promote gastric cancer (GC) proliferation and invasion, while four and a half LIM domains 1 (FHL1) involves GC cells apoptosis. We attempted to address inter-relationship between CCDC43 and FHL1 in modulating GC cells growth and apoptosis. Levels of protein expression were assessed by western blot, immunofluorescence. Using EdU, plate colony formation, Matrigel invasion and animal models, we evaluated the function in vitro and in vivo. Apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Reciprocal co-immunoprecipitation (co-IP) analyses indicated that CCDC43 physically interacted with FHL1. The expression of CCDC43 was negatively correlated with FHL1. Moreover, up-regulation of CCDC43 resulted in FHL1 level decline, and the reverse is also true. CCDC43 expressed jointly with FHL1 group significantly decreases the ability of the growth, metastasis and invasion of GC cells compared with that of the CCDC43 group. Furthermore, siRNA-mediated repression of CCDC43 results in dissociation from FHL1 and causes suppression of GC cell proliferation and metastasis. CCDC43 repression mediates the stability of FHL1 protein. In addition, CCDC43 interacts with FHL1. Knockdown of CCDC43 plus FHL1 overexpression inhibits proliferation and migration and induces apoptosis of GC cells in vitro and vivo.

In this article, we have proposed and demonstrated a new approach to implementing microwave photonic filter (MPF) with switchable, tunable and reconfigurable passbands based on a multi-wavelength fiber laser (MWFL) cooperating with a fiber Mach–Zehnder interferometer (FMZI). An EDFA and an SOA have been employed as a hybrid gain medium in the laser cavity, to suppress the homogeneous broadening of EDF. By inserting the FMZI in the fiber laser cavity, MWFL with tunable and switchable wavelength spacing has been achieved, which can be used as the multi-wavelength optical source to implement switchable, tunable and reconfigurable MPF together with a dispersive medium. By tuning the length of variable optical delay line (VODL), the wavelength spacing of the MWFL can be changed, and thus the passband’s central frequency of the MPF. By adjusting the polarization states, gain of EDFA or SOA of the laser cavity, the shape of the laser output can be adjustable, and as a result, shape-adjustable passbands of the MPF have been realized. By introducing the reflective FMZI structure as the wavelength selective component and carefully adjusting the polarization states, half number of the passband can be suppressed, which means the MPF can be switchable. The proposed MPF exhibits shape-adjustable and switchable passbands and enjoys more flexibility compared to previous methods.

Background The deubiquitinating enzyme ubiquitin-specific protease 3 (USP3) plays a crucial role in numerous biological processes. The aberrant expression of USP3 may have an important role in tumor development. However, the mechanism by which USP3 promotes gastric cancer (GC) metastasis remains largely unknown. Methods Effects of USP3 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated utilizing proteomics, RT-PCR, western blotting, immunohistochemistry, immunofluorescence, cell invasion and migration assays and xenograft tumor models. Results USP3 expression was upregulated in GC compared with matched normal tissues and was predictive of poor survival. USP3 also promoted migration and epithelial-to-mesenchymal transition (EMT) in GC cells. Moreover, TGF-β1 induced USP3 expression, and USP3 knockdown inhibited TGF-β1-induced EMT. Furthermore, we utilized Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) to identify differentially expressed proteins in USP3-overexpressing cells compared with control cells. Importantly, we found that SUZ12 is indispensable for USP3-mediated oncogenic activity in GC. We observed that USP3 interacted with and stabilized SUZ12 via deubiquitination. SUZ12 knockdown inhibited USP3-induced migration and invasion, as well as EMT in GC cells. Examination of clinical samples confirmed that USP3 expression was positively correlated with SUZ12 protein expression and that the levels of USP3 or SUZ12 protein were negatively correlated with the levels of E-cadherin protein. Conclusions These findings identify USP3 as a critical regulator. The USP3-SUZ12 axis might promote tumor progression and could be a potential therapeutic candidate for human GC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1270-4) contains supplementary material, which is available to authorized users.

The development of malignant tumors is a series of complex processes, the majority of which have not been elucidated. The aim of the present study was to investigate the microRNAs (miRNAs/miR) that affect the migration and invasion abilities of CRC cells. Our previous reports have revealed that miR‑500a‑5p suppressed CRC cell growth and malignant transformation. The present study demonstrated that overexpression of miR‑500a‑5p reduced the expression of vimentin, while increasing the expression of E‑cadherin. Inhibition of miR‑500a‑5p resulted in spindle‑like morphological changes and reorganization of F‑actin in CRC cells. Furthermore, miR‑500a‑5p attenuated the transforming growth factor‑β signaling pathway in EMT. Additionally, emodin inhibited the miR‑500a‑5p inhibitor and suppressed the EMT process. In animal models of metastasis using nude mice, EMT and LoVo cell metastasis was modulated by miR‑500a‑5p. Therefore, the findings of the present study demonstrated that miR‑500a‑5p is associated with a positive therapeutic outcome in terms of invasion/migration of CRC cells and mesenchymal‑like cell changes.

In this paper, a continuously tunable microwave photonic filter (MPF) with optical frequency comb generated by recirculating frequency shifter (RFS) based on an IQ modular is proposed and experimentally demonstrated. The optical comb generated by the proposed scheme possess good flatness and high optical signal to noise ratio. Optical frequency comb with 63 comb lines can be obtained by RFS based on the single-sideband recirculating frequency shifter (SSB-RFS) scheme, by employing the optical filter with bandwidth of 10 nm and the modulation microwave signal with the frequency of 20 GHz. In addition, the modulation depth of the stable optical frequency comb exceeds 15dB, and the flatness fluctuation of optical frequency is less than 3dB. MPF with narrow bandwidth passbands has been implemented by taking the generated optical frequency comb as the optical source together with a dispersive medium. By changing the frequency of the modulation signal, the number and wavelength interval of optical frequency comb can be changed. As a result, the free spectrum range (FSR) and bandwidth of the MPF can be tuned and in our experiment the central frequencies of two passbans of the MPF has been tuned linearly from 7.38 GHz to 11.30 GHz, and 14.65 GHz to 19.53 GHz, respectively. © 2020 The Author(s)

In human gastric cancer (GC), the upregulation of FOXK1 and vimentin is frequently observed in cancer cells and correlates with increased malignancy. We report that FOXK1 synergizes with vimentin to promote GC invasion and metastasis via the induction of epithelial-mesenchymal transition (EMT). We showed that higher expression levels of FOXK1 were significantly associated with GC development. FOXK1 can physically interact with and stabilize vimentin. Moreover, a positive correlation between the expression of FOXK1 and vimentin was found in GC cells. Higher expression levels of these two proteins were significantly associated with differentiation, lymph node metastasis, AJCC stage, and poorer prognosis. Furthermore, the coexpression of FOXK1 and vimentin enhances cell metastasis through the induction of EMT in GC cells. However, the siRNA-mediated repression of vimentin in FOXK1-overexpressing cells reversed the EMT-like phenotype and reduced GC cell migration and invasion in vitro and in vivo. Altogether, our findings suggest that the vimentin-FOXK1 axis provides new insights into the molecular mechanisms underlying EMT regulation during GC progression and metastasis.

The multi-passband microwave photonic filter (MPF) with flexible passband selection based on a second-order Solc-Sagnac interferometer and dispersive medium is proposed and experimentally demonstrated. The second-order Solc-Sagnac interferometer is used as the spectrum slicer of the MPF, and by adjusting polarization controllers (PCs) inside the interferometer, the passband can be flexibly selected. Two output port of the optical coupler (OC) are connected with two sections of polarization maintaining optical fiber (PMF) and two PCs to form the second-order Solc-Sagnac interferometer. PMF with different length results in different FSR of the interferometer pattern of Sagnac interferometer and thus different frequency of the MPF’s passband. By adjusting PCs in the second-order Solc-Sagnac interferometer, the visibility of the corresponding interference patterns can be changed, and as a result the passband of the MPF can be selected. In our experiment, by carefully adjusting the PCs in the Sagnac loop, multi-passband MPF with three selectable passbands has been implemented, whose passbands are located at the frequency of 0.219 GHz, 0.451 GHz, and 0.651 GHz, respectively when the length of two PMFs are 1 m and 2 m. In addition, we can also obtain MPF with flexible switching between single passband, double passbands and three passbands, respectively. And by designing the length of the PMFs in the second-order Solc-Sagnac interferometer, passbands at higher frequency can be realized, e.g. in our experiment, by using PMFs with the length of 2 m and 4 m, MPF with switchable passbands at 0.435 GHz, 0.877 GHz, 1.318 GHz has been realized, and the suppression ratio of the MPF is more than 25 dB.

In this paper, we have proposed and experimentally demonstrated a multiplexed sensing interrogation technique based on a flexibly switchable multi-passband RF filter with a polarization maintaining fiber (PMF) Solc-Sagnac loop. A high-order Solc-Sagnac loop can be used as a spectrum slicer as well as sensing heads, and a multi-passband microwave photonic filter (MPF) can be achieved together with a dispersive medium. Environmental parameter variations will cause a frequency shift of the corresponding passband of the MPF, so by employing only one Sagnac loop, it is possible to monitor several environmental parameters simultaneously. In this article, we have demonstrated and analyzed the performance of the flexibly switchable multi-passband MPF by using a second-order Solc-Sagnac loop. To demonstrate the temperature sensing capabilities of our interrogation system, we have applied temperature changes individually to Sensor Head 1 ( L P M F 1 ≈ 0.97 m ) only, Sensor Head 2 ( L P M F 2 ≈ 2.97 m ) only, and both Sensor Head 1 and 2 in the experiment. By monitoring frequency shift of the MPF’s passbands, the sensitivities for Sensor Head 1 and Sensor Head 2 have been estimated to be -0.275 ± 0.011 MHz/℃ and -0.811 ± 0.013 MHz/℃ respectively, which show a good sensing linearity and stability. By utilizing the longer length of the sensing PMF, higher sensitivity can be achieved. By using Solc-Sagnac loop with higher order, more sensors can be multiplexed.

A novel half-side PDMS-coated photonic crystal fiber (PCF) sensor based on surface plasmon resonance (SPR) is proposed for simultaneous detection of seawater salinity and temperature. The plasmonic material gold is coated on the outer surface of the PCF to measure the seawater salinity by exciting SPR effect. Moreover, the polydimethylsiloxane (PDMS) layer is coated on the upper half-side of the surface of the sensor as an independent temperature sensing channel. The properties of modes coupling between surface plasmon polaritons (SPPs) mode and four different core modes are investigated. Meanwhile, the influence of various geometrical parameters on the sensing characteristics are theoretically simulated by using finite element method (FEM). The numerical results show that the salinity sensitivity of the designed sensor can reach 0.307 nm/‰ with a resolution of 0.3257‰. Additionally, the temperature sensitivity of −4.937 nm/°C with the resolution of 0.0203 °C in the sensing range from 25 °C to 50 °C has been obtained. The proposed sensor, possessing advantages such as ease of fabrication, excellent sensing performance and low cost, not only realizes the simultaneous measurement of two parameters, but also has potential in the field of seawater monitoring.

Table S1. Correlation between USP3 protein expression and the clinicopathological parameters of GC. Table S2. iTRAQ ratios of down-regulated proteins in GC tissues. Supplementary materials and methods. (DOCX 53 kb)

Supplementary Materials and Methods. Table S1. Primary Primers Used in This Study. (DOCX 23 kb)

Background: Previous studies have showed an association of coiled-coil domain-containing (CCDC) genes with cancers. Our studies also found that CCDC43 is highly expressed in colorectal cancer. However, the expression patterns and molecular mechanisms of CCDC43 in gastric cancer (GC) have not been elucidated. Methods: We analyzed the CCDC43 gene expression in GC samples and adjacent noncancerous mucosa tissues by immunohistochemistry, western blot and quantitative real-time PCR (qPCR) analysis. Additionally, we utilized isobaric Tag for Relative and Absolute Quantitation (iTRAQ) to identify differentially expressed proteins in CCDC43-overexpressing cells. Chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay were used to investigate the role of transcription factor YY1 in promoting the expression of CCDC43 and ADRM1. Findings: CCDC43 was overexpressed in gastric tissues. CCDC43 expression was closely related to tumor differentiation, lymph-node-metastasis and prognosis of gastric cancer. Over-expression of CCDC43 promoted the proliferation, invasion and metastasis of GC cells. CCDC43 could upregulate and stabilize ADRM1, resulting in the degradation of ubiquitin-mediated proteasomal. While, inhibition of ADRM1 could reverse the function of CCDC43 in GC both in vitro and in vivo. In addition, our data demonstrated that transcription factor YY1 directly bound to the CCDC43 gene promoter, leading to over-expression of CCDC43 and ADRM1. We also confirmed that YY1, CCDC43 and ADRM1 proteins were positively and correlatively expressed in human GC tissue compared with adjacent noncancerous tissues. Interpretation: Our findings suggest that the YY1-CCDC43-ADRM1 axis provides a potential therapeutic target of GC. Funding: Natural Science Foundation of China. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: Samples from surgical removal of gastric cancer from 2019 were selected from the Department of Surgery of Nanfang Hospital, Southern Medical University. The Ethics Committee of the Southern Medical University, China, approved our experimental protocols. Mice were maintained in a specific pathogen-free environment. All in vivo experiments were approved by the Institutional Animal Care and Use Committee of Southern Medical University.

Background: The transcription factor HOXD9 is one of the members of the HOX family, which plays an important role in neoplastic processes. However, the role of HOXD9 in the growth and metastasis of gastric cancer (GC) remains to be elucidated. Methods: In vitro functional role of HOXD9 and RURY3 in GC cells was determined using the TMA-based immunohistochemistry, western blot, EdU incorporation, gelatin zymography, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. In vivo tumour growth and metastasis were conducted in nude mice. Findings: HOXD9 is overexpressed in GC cells and tissues. The high expression of HOXD9 was correlated with poor survival in GC patients. Functionally, HOXD9 expression significantly promoted the proliferation, invasion and migration of GC cells. Mechanically, HOXD9 directly associated with the RUFY3 promoter to increase the transcriptional activity of RUFY3. Inhibition of RUFY3 attenuated the proliferation, migration and invasiveness of HOXD9-overexpressing GC cells in vitro and in vivo. Moreover, both HOXD9 and RUFY3 were highly expressed in cancer cells but not in normal gastric tissues, with their expressions being positively correlated. Interpretation: The evidence presented here suggests that the HOXD9-RUFY3 axis promotes the development and progression of human GC. Funding Statement: This study was supported by grants from the National Natural Science Funds of China (Nos.81672875 and 81772964). The funding organization: the Guangzhou Pilot Project of the Clinical and Translational Research Center (early gastrointestinal cancer, No.7415696196402). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was reviewed and approved by the Medical Ethics Committee of Nanfang Hospital (NFEC-2017-062), Southern Medical University, Guangzhou, China. All animal studies were approved by the Institutional Animal Care and Use Committee of Committee of Nanfang Hospital.