The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China.

BACKGROUND: Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms. METHODS: This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms. FINDINGS: Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms. INTERPRETATION: Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effects of lobectomy versus sub-lobar resection on the survival in adults with stage IA left upper lobe non-small cell lung cancer: a retrospective cohort study based on the SEER database.

INTRODUCTION: To compare the survival after lobectomy (LR) and sub-lobar resection (SLR) of left upper lobe (LUL) among non-small cell lung cancer (NSCLC) patients with stage IA. METHODS: This retrospective cohort research analyzed public data collected by the Surveillance, Epidemiology, and End Results (SEER) database. Tumor characteristics were determined based on the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3). Propensity score matching (PSM) analysis was performed with a ratio of 1:1. Univariate and multivariable Cox proportional regression analyses were used to assess the effects of LR and SLR on the survival of the patients, with hazard ratios (HRs) and 95% confidence intervals (95%CIs). The effects were further evaluated by different subgroups of age, gender, tumor grades, histologic types, T stages. RESULTS: Of the total 2,649 patients, 1,907 underwent the LR and 742 received SLR. Totally 998 patients died at the end of the follow-up. The median survival time of all patients were 66 (49, 87) months. After adjusting the age, gender, race, tumor grade, histologic type, T stage, examined lymph nodes, radiation, and chemotherapy, NSCLC patients with stage IA who received SLR had higher odds of death in comparison with these patients who received LR (HR=1.424, 95%CI: 1.227-1.652). After PSM, SLR was associated with higher odds of death in the patients (HR=1.35, 95%CI: 1.10-1.66). Similar results were discovered in different subpopulations. DISCUSSION/CONCLUSION: The SLR was inferior to LR on the survival of NSCLC patients with stage IA.

A small-sized tube versus traditional closed thoracic drainage in uniportal thoracoscopic surgery.

Introduction: To assess the feasibility and safety of placing a small-sized tube as drainage in patients after uniportal thoracoscopic lung resection. Patients and Methods: Patients who received uniportal video-assisted thoracoscopic surgery (U-VATS) lung resection were identified in our database. Patients placed small-sized tube drainage were compared with those placed conventional chest tube in terms of characteristics, operation modality, post-operative pulmonary complications, post-operative pain, chest tube duration and post-operative hospital stay. Propensity score matching was performed. Results: Of the 217 enrolled patients, 173 were assigned to the conventional tube group and 44 were assigned to the small-sized tube group. Rates of post-operative pulmonary complications were relatively low and similar between the two groups. After propensity score matching, operation duration was shorter (1 h vs. 1.21 h, P = 0.01) was shorter, and the maximum value of the Visual Analogue Scale (VAS) score after operation (1 vs. 1.5, P = 0.02) and the overall average value of VAS score after operation (0.33 vs. 0.88, P = 0.006) was lower in small-sized tube group. No significant difference was observed in chest tube duration (2 vs. 2, P = 0.34) and post-operative hospital stay (3 vs. 3, P = 0.34). Conclusions: Compared to conventional chest tubes, small-sized tubes for post-operative drainage after U-VATS lung resection may be a safe and promising approach for reducing post-operative pain.

Clinical efficacy and safety of adjuvant EGFR-TKIs for resected stage IB lung adenocarcinoma: A real-world study based on propensity score matching.

BACKGROUND: Adjuvant therapy for stage IB non-small cell lung cancer remains debatable. In this real-world study, we evaluate the efficacy and safety of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for resected stage IB lung adenocarcinoma. METHODS: This real-world study recruited 249 patients diagnosed with stage IB disease after surgical resection between January 2013 and September 2021. Sixty-six (26.5%) patients received adjuvant targeted therapy (TKIs group), and 183 (73.5%) were enrolled in the clinical observation (CO) group. Propensity scores were matched to minimize the observed confounder effects between the two groups, and 59 patient pairs were matched. The primary endpoint was disease-free survival (DFS). RESULTS: In the TKI group, 38 (64.4%) patients chose to receive icotinib, 27.1% (16/59) received gefitinib, and 5 patients (8.5%) chose osimertinib. The median follow-up time was 30.8 months (range: 7-107 months). Two (3.4%) patients in the TKI group and 10 (16.9%) in the CO group experienced disease relapse. The 3-year DFS rates were 98.3% in the TKI group and 83.0% in the CO group (HR: 0.10; 95% CI: 0.01-0.78; p = 0.008). DFS differences were found in the entire cohort (p = 0.005) and the matched cohort (p = 0.024) between the two groups. Multivariate analysis showed that adjuvant EGFR-TKIs was an independent factor for DFS (HR: 0.211; 95% CI: 0.045-0.979; p = 0.047), along with poor cell differentiation (HR: 5.256; 95% CI: 1.648-16.769; p = 0.005), and spread through air spaces (HR: 5.612; 95% CI: 1.137-27.700; p = 0.034). None of the patients discontinued EGFR-TKIs owing to the low occurrence rate of treatment-related serious adverse events. CONCLUSION: Adjuvant EGFR-TKIs could significantly improve DFS among patients with stage IB lung adenocarcinoma compared with CO, with a safe and tolerable profile.

Uniportal video-assisted anatomical segmentectomy: an analysis of the learning curve.

BACKGROUND: This study aimed to demonstrate the learning curve of anatomical segmentectomy performed by uniportal video-assisted thoracoscopic surgery (U-VATS). METHOD: We conducted a retrospective study of U-VATS segmentectomies performed by the same surgeon between September 2019 and August 2022. The learning curve was demonstrated using risk-adjusted cumulative sum (RA-CUSUM) analysis in terms of perioperative complications, which reflected surgical quality and technique proficiency. The surgical outcomes were also compared between different phases. RESULT: The complication-based learning curve of U-VATS segmentectomy could be divided into two phases based on RA-CUSUM analysis: phase I, the initial learning phase (cases 1-50) and phase II, the proficiency phase (cases 51-141). Significantly higher complication rates (24.0 vs. 8.8%, p=0.013), longer surgical times (119.8±31.9 vs. 106.2±23.8 min, p=0.005), and more blood loss (20 [IQR, 20-30] vs. 20 [IQR, 10-20] ml, p=0.003) were observed in phase I than in phase II. CONCLUSION: The learning curve of U-VATS segmentectomy consists of two phases, and at least 50 cases were required to gain technique proficiency and achieve high-quality surgical outcomes.

PSMD3-ILF3 signaling cascade drives lung cancer cell proliferation and migration.

BACKGROUND: Proteasome 26S subunit, non-ATPase 3 (PSMD3) has been reported to participate in various human cancers. Nevertheless, the function of PSMD3 in lung cancer (LC) remains unclear. METHODS: RT-qPCR and western blot were used to detect the expression of PSMD3 in LC tissues form TCGA database and clinical samples, and LC cell lines. To study the effect of PSMD3 on LC cell proliferation, migration, invasion, and apoptosis, siRNAs targeting PSMD3 were synthesized and overexpressed plasmids were constructed. CCK-8 assay, Transwell assay, and etc. were used to evaluate the results. Tumor xenograft model was used to evaluate the function of PSMD3 on tumor growth. CO-IP and MS were used to scan the proteins that bind with PSMD3. The interaction between PSMD3 and ILF3 in lung cancer cells were studied using IF staining, CHX protein stability, and ubiquitination assay. Additionally, the effect of ILF3 on cell progression and LC tumor growth was demonstrated by conducting a recovery assay using siILF3 and an ILF3 inhibitor YM155. RESULTS: We observed that PSMD3 was significantly overexpressed in LC tissues and cells, which indicated a poor prognosis. Meanwhile, we found that PSMD3 promoted cell proliferation, migration, and invasion of LC cells. We also determined that PSMD3 stabilized the protein expression of ILF3 and the deubiquitination of ILF3 in lung cancer cells. Furthermore, animal experiments showed that the ILF3 inhibitor YM155 could suppress tumor growth with the presence of PSMD3. CONCLUSIONS: PSMD3 collectively regulated the stability of ILF3 protein and facilitated the ubiquitination of endogenous ILF3 in LC, which ultimately promoted the progression of LC cells. The PSMD3/ ILF3 axis could potentially be used as a novel strategy for both diagnosis and treatment of LC.

HPIP is an essential scaffolding protein running through the EGFR-RAS-ERK pathway and drives tumorigenesis.

The EGFR-RAS-ERK pathway plays a key role in cancer development and progression. However, the integral assembly of EGFR-RAS-ERK signaling complexes from the upstream component EGFR to the downstream component ERK is largely unknown. Here, we show that hematopoietic PBX-interacting protein (HPIP) interacts with all classical components of the EGFR-RAS-ERK pathway and forms at least two complexes with overlapping components. Experiments of HPIP knockout or knockdown and chemical inhibition of HPIP expression showed that HPIP is required for EGFR-RAS-ERK signaling complex formation, EGFR-RAS-ERK signaling activation, and EGFR-RAS-ERK signaling-mediated promotion of aerobic glycolysis as well as cancer cell growth in vitro and in vivo. HPIP expression is correlated with EGFR-RAS-ERK signaling activation and predicts worse clinical outcomes in patients with lung cancer. These results provide insights into EGFR-RAS-ERK signaling complex formation and EGFR-RAS-ERK signaling regulation and suggest that HPIP may be a promising therapeutic target for cancer with dysregulated EGFR-RAS-ERK signaling.

Clinicopathological and survival outcomes of 4L lymph node dissection in left lung adenocarcinoma and squamous cell carcinoma.

Background: Whether 4L lymph node dissection (LND) should be performed remains unclear and controversial. Prior studies have found that station 4L metastasis was not rare and that 4L LND may provide survival benefits. The objective of this study was to analyze the clinicopathological and survival outcomes of 4L LND from the perspective of histology. Methods: This retrospective study included 74 patients with squamous cell carcinoma (SCC) and 84 patients diagnosed with lung adenocarcinoma (ADC) between January 2008 and October 2020. All patients underwent pulmonary resection with station 4L LND and were staged as T1-4N0-2M0. Clinicopathological features and survival outcomes were investigated based on histology. The study endpoints were disease-free survival (DFS) and overall survival (OS). Results: The incidence rate of station 4L metastasis was 17.1% (27/158) in the entire cohort, with 8.1% in the SCC group, and 25.0% in the ADC group. No statistical differences in the 5-year DFS rates (67.1% vs. 61.7%, P=0.812) and 5-year OS rates (68.6% vs. 59.3%, P=0.100) were observed between the ADC group and the SCC group. Multivariate logistic analysis revealed that histology (SCC vs. ADC: OR, 0.185; 95% CI, 0.049-0.706; P=0.013) was independently associated with 4L metastasis. Multivariate survival analysis showed that the status of 4L metastasis was an independent factor for DFS (HR, 2.563; 95% CI, 1.282-5.123; P=0.008) but not for OS (HR, 1.597; 95% CI, 0.749-3.402; P=0.225). Conclusion: Station 4L metastasis is not rare in left lung cancer. Patients with ADC have a greater predilection for station 4L metastasis and may benefit more from performing 4L LND.

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study.

Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next-generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7-27.0 months). ctDNA-positive or -negative patients with tumors of any stage had similar disease-free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non-tissue derived. Patients with detectable postoperative ctDNA with tissue-derived mutations had comparable DFS with those with non-tissue-derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.

Assessment of preoperative anxiety and depression in patients with pulmonary ground-glass opacities: Risk factors and postoperative outcomes.

Objective: A large number of patients with pulmonary ground-glass opacities (GGOs) have anxiety and depression. However, the contributing factors and effects of anxiety and depression on postoperative outcomes are still unclear. Methods: Clinical data for patients undergoing surgical resection for pulmonary GGOs were collected. We prospectively evaluated levels and risk factors for anxiety and depression in patients with GGOs before surgery. The relationship between psychological disorders and postoperative morbidity was evaluated. Quality of life (QoL) was also assessed. Results: A total of 133 patients were enrolled. Prevalence rates of preoperative anxiety and depression were 26.3% (n = 35) and 18% (n = 24), respectively. Multivariate analysis revealed depression [odds ratio(OR) = 16.27, p < 0.001] and multiple GGOs (OR = 3.146, p = 0.033) to be risk factors for preoperative anxiety. Anxiety (OR = 52.166, p < 0.001), age > 60 (OR = 3.601, p = 0.036), and unemployment (OR = 8.248, p = 0.006) were identified as risk factors for preoperative depression. Preoperative anxiety and depression were associated with lower QoL and higher postoperative pain scores. Our results also revealed that the incidence of postoperative atrial fibrillation was higher in patients with than in those without anxiety. Conclusions: In patients with pulmonary GGOs, comprehensive psychological assessment and appropriate management are required before surgery to improve QoL and reduce postoperative morbidity.

Long-term results of postoperative unsuspected small cell lung cancer on real-world data.

BACKGROUND: In traditional opinion, solid pulmonary nodule suspected lung cancer should be confirmed by pathology before the operation to exclude small cell lung cancer (SCLC), considering SCLC tends to be aggressive and surgical effect in the management of SCLC remains controversial. The aim of this study was to evaluate the survival result and risk factors of postoperative unsuspected SCLC. METHODS: A total of 120 patients with postoperative unsuspected SCLC who were confirmed by pathology and referred to Chinese PLA General Hospital between 2000 and 2021 were retrospectively analyzed (surgery group). Additionally, 120 patients with limited-stage SCLC who underwent chemotherapy and radiotherapy in the same period were enrolled in the chemoradiotherapy group.. Kaplan-Meier method was used to estimate survival; the Log-Rank test was used to compare survival rates between different groups; a COX stepwise regression model was used for multivariate analysis. RESULTS: Among 120 patients in the surgery group, 28 were with central type and other 92 with peripheral type. The median survival (OS) was 44.85 months, and the 5-year survival rate was 46%. The 5-year survival rates for stage I, II, and III were 52.1%, 45.4%, and 27.8%, respectively. The mean disease-free survival time (DFS) was 30.63 ± 4.38 months, and the 5-year DFS rate was 31.5%. In the chemoradiotherapy group, the mean OS was 21.4 ± 4.26 months, and the 5-year survival rate was 28.3%. The 5-year survival rates for clinical stage I, II, and III were 42.5%, 39.8%, and 20.5%, respectively. The mean progression-free survival (PFS) was 10.63 ± 3.6 months. In the surgery group, one-way ANOVA revealed that the gender, symptoms, smoking history, tumor location, and postoperative radiotherapy were not associated with OS (P ≥ 0.05), while age, surgical approach, surgical method, N stage, TNM stage, and vascular tumor thrombus were related to OS (P < 0.05). Multivariate analysis indicated that the N stage was associated with OS (HR = 1.86 P = 0.042). CONCLUSION: Surgery and adjuvant therapy were found to have encouraging outcomes in postoperative unsuspected SCLC. Patients with stage I, stage II and part of stage IIIA SCLC could benefit from surgery and the standard lobectomy, and systematic lymph node dissection, is also recommended for these patients.

A signal recognition particle-related joint model of LASSO regression, SVM-RFE and artificial neural network for the diagnosis of systemic sclerosis-associated pulmonary hypertension.

Background: Systemic sclerosis-associated pulmonary hypertension (SSc-PH) is one of the most common causes of death in patients with systemic sclerosis (SSc). The complexity of SSc-PH and the heterogeneity of clinical features in SSc-PH patients contribute to the difficulty of diagnosis. Therefore, there is a pressing need to develop and optimize models for the diagnosis of SSc-PH. Signal recognition particle (SRP) deficiency has been found to promote the progression of multiple cancers, but the relationship between SRP and SSc-PH has not been explored. Methods: First, we obtained the GSE19617 and GSE33463 datasets from the Gene Expression Omnibus (GEO) database as the training set, GSE22356 as the test set, and the SRP-related gene set from the MSigDB database. Next, we identified differentially expressed SRP-related genes (DE-SRPGs) and performed unsupervised clustering and gene enrichment analyses. Then, we used least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) to identify SRP-related diagnostic genes (SRP-DGs). We constructed an SRP scoring system and a nomogram model based on the SRP-DGs and established an artificial neural network (ANN) for diagnosis. We used receiver operating characteristic (ROC) curves to identify the SRP-related signature in the training and test sets. Finally, we analyzed immune features, signaling pathways, and drugs associated with SRP and investigated SRP-DGs' functions using single gene batch correlation analysis-based GSEA. Results: We obtained 30 DE-SRPGs and found that they were enriched in functions and pathways such as "protein targeting to ER," "cytosolic ribosome," and "coronavirus disease-COVID-19". Subsequently, we identified seven SRP-DGs whose expression levels and diagnostic efficacy were validated in the test set. As one signature, the area under the ROC curve (AUC) values for seven SRP-DGs were 0.769 and 1.000 in the training and test sets, respectively. Predictions made using the nomogram model are likely beneficial for SSc-PH patients. The AUC values of the ANN were 0.999 and 0.860 in the training and test sets, respectively. Finally, we discovered that some immune cells and pathways, such as activated dendritic cells, complement activation, and heme metabolism, were significantly associated with SRP-DGs and identified ten drugs targeting SRP-DGs. Conclusion: We constructed a reliable SRP-related ANN model for the diagnosis of SSc-PH and investigated the possible role of SRP in the etiopathogenesis of SSc-PH by bioinformatics methods to provide a basis for precision and personalized medicine.

Comprehensive Analysis of a Novel Immune-Related Gene Signature in Lung Adenocarcinoma.

Lung cancer is the major cause of cancer-related deaths around the world. Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, contributed to the majority of mortalities and showed different clinical outcomes in prognosis. Tumor-infiltrated immune cells at the tumor site are associated with better survival and immunotherapy response. Thus, it is essential to further investigate the molecular mechanisms and new prognostic biomarkers of lung adenocarcinoma development and progression. In this study, a six-gene signature (CR2, FGF5, INSL4, RAET1L, AGER, and TNFRSF13C) was established to predict the prognosis of LUAD patients, as well as predictive value. The prognostic risk model was also significantly associated with the infiltration of immune cells in LUAD microenvironments. To sum up, a novel immune-related six-gene signature (CR2, FGF5, INSL4, RAET1L, AGER, and TNFRSF13C) was identified that could predict LUAD survival and is highly related to B cells and dendritic cells, which may provide a theoretical basis of personalized treatment for targeted immunotherapy.

The Predictive Value of Stair Climbing Test on Postoperative Complications in Lung Cancer Patients with Limited Pulmonary Function.

PURPOSE: To evaluate the predictive value of stair climbing test (SCT) on postoperative complications in lung cancer patients with limited pulmonary function. METHODS: A total of 727 hospitalized lung cancer patients with limited pulmonary function were retrospectively reviewed. Included in the cohort were 424 patients who underwent SCT preoperatively. Patients were grouped according to general condition, past medical history, surgical approach, pulmonary function test, and SCT results. Comparison of the postoperative cardiopulmonary complication rates was made and independent risk factors were identified. RESULTS: A total of 89 cardiopulmonary-related complications occurred in 69 cases, accounting for 16.3% of the entire cohort. The postoperative cardiopulmonary complication rates were significantly different between groups stratified by smoking index, percentage of forced expiratory volume in one second, percentage of diffusion capacity for carbon monoxide, SCT results, excision extension, and anesthetic duration (p <0.05). Multivariate analysis showed that only height achieved (p <0.001), changes in heart rate (∆HR; p <0.001), and excision extension (p = 0.006) were independent risk factors for postoperative cardiopulmonary complications. CONCLUSIONS: The SCT could be used as a preoperative screening method for lung cancer patients with limited pulmonary function. For those patients who could only climb less than 6 floors or had ∆HR >30 bpm in the test, sublobar resection should be selected to reduce the postoperative cardiopulmonary complication rate.

E2F1-activated LINC01224 drives esophageal squamous cell carcinoma cell malignant behaviors via targeting miR-6884-5p/DVL3 axis and activating Wnt/ß-catenin signaling pathway.

Current evidence has unveiled that long non-coding RNAs (lncRNAs) are pivotal regulators in the development of cancers. This study aimed to investigate the potential mechanisms of LINC01224 in esophageal squamous cell carcinoma (ESCC) cells. RT-qPCR analysis was done to test LINC01224 expression in ESCC cells. Functional assays were conducted to assess the influences of LINC01224 on ESCC cell functions. Mechanism assays were carried out to detect the regulatory mechanisms of LINC01224 at post-transcriptional and transcriptional levels. Briefly, LINC01224 expression was remarkably high in ESCC cells. LINC01224 silence restricted the proliferative, migratory, and invasive capabilities of ESCC cells. Moreover, LINC01224 could combine with miR-6884-5p by acting as a ceRNA. Further, DVL3 was proved to be targeted by miR-6884-5p. Importantly, LINC01224 could switch on Wnt/ß-catenin signaling pathway by via enhancing DVL3 expression. Additionally, E2F1 could serve as a transcription factor to stimulate LINC01224 transcription. In summary, our study elucidated that E2F1-activated LINC01224 regulated miR-6884-5p/DVL3 to actuate the Wnt/ß-catenin signaling pathway, which facilitates multiple phenotype of ESCC cells, including proliferation, migration, and invasion. Our findings might offer potential therapeutic targets for ESCC treatment.

Downregulated RPL6 inhibits lung cancer cell proliferation and migration and promotes cell apoptosis by regulating the AKT signaling pathway.

Background: Lung cancer is still one of the most common causes of cancer-related mortality, and the overall survival is less than 5%. It is important and necessary to elucidate the mechanism of lung cancer progression. Recently, more and more research has demonstrated that many ribosomal proteins (RPs) are dysregulated in tumors. Among these RPs, ribosomal protein L6 (RPL6) is reported to promote cell growth and cell cycle progression in gastric cancer cells through upregulating cyclin E. However, its function in lung cancer is still unknown. Methods: We first explored RPL6 expression in lung cancer samples. Next, we used gene knockdown to analyze the unknown regulatory role of RPL6 in lung cancer carcinoma and lung cancer cell lines. Furthermore, we explored the potential signaling pathway of RPL6 with Western blotting. Results: In this study, we demonstrated that RPL6 expression was highly expressed in lung cancer tissues and lung cancer cell lines. RPL6 downregulation inhibited H1299 and H2975 cell proliferation, migration and induced cell apoptosis. Also RPL6 downregulation increased the protein levels of cleaved caspase-3 and Bax, while decreasing the protein level of B-cell lymphoma 2 (Bcl-2). Western blotting results showed that proteins activating the AKT signaling pathway, such as p-AKT and p-S6, were downregulated in RPL6 knockdown lung cancer cells. Conclusions: These findings show that RPL6 can be used as a potential therapeutic and preventive biomarker in lung cancer treatment and prognosis by regulating the AKT signaling pathway.