ABSTRACT
BACKGROUND: Chaperonin containing TCP1 subunit 3 (CCT3) acts as an oncogene in cancers, whereas its role and underlying mechanisms in lung adenocarcinoma (LUAD) are poorly understood. This study investigated the clinical relevance and function of CCT3 in LUAD. METHODS: Clinical relevance of CCT3 in LUAD and lung squamous cell carcinoma (LUSC) was analyzed based on TCGA database. qRT-PCR and Western blot were used to detect mRNA and protein expression, respectively. CCK8 and colony formation were performed to measure cell viability. PI and PI/Annexin V-FITC assay kit was used to determine cell cycle and cell death, respectively. Luciferase activity was performed to check whether CCT3 regulated slc7a11's transcription activity. Ferroptosis was determined by incubating the cells with ferroptosis and apoptosis inducer, their inhibitor and autophagy inhibitor, followed by cell viability examination. RESULTS: We found that CCT3 was overexpressed in LUAD and LUSC tissues. Overexpression of CCT3 predicted the poor prognosis of LUAD patients. Loss-of-function and gain-of-function experiments demonstrated that CCT3 promoted the proliferation and colony formation of LUAD cells. In addition, CCT3 promoted cell cycle progression and suppressed slc7a11-mediated cell ferroptosis, but not apoptosis. We also found that CCT3 activated AKT. MK2206 significantly reduced the viability of CCT3 overexpressed LUAD cells, while had smaller inhibitory effect on the proliferation of control cells, suggesting that CCT3 dictates the sensitivity of LUAD cells to AKT inhibition. CONCLUSION: Our study demonstrates that CCT3 contributes to the proliferation and growth of LUAD cells through inhibition of ferroptosis and activation of AKT.
Subject(s)
Adenocarcinoma of Lung , Chaperonin Containing TCP-1 , Ferroptosis , Lung Neoplasms , Proto-Oncogene Proteins c-akt , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Chaperonin Containing TCP-1/genetics , Chaperonin Containing TCP-1/metabolism , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Up-RegulationABSTRACT
INTRODUCTION: We evaluated the feasibility and efficacy of chemoradiotherapy with concurrent regional arterial chemotherapy (CRT/RAC) for locally bulky unresectable rectal cancer (LBURC). CASE PRESENTATION: We retrospectively reviewed 9 patients with LBURC who received CRT/RAC between January 2012 and December 2018. The regimen consisted of chemoradiotherapy and 3 cycles of regional arterial chemotherapy. Surgery was performed 6 weeks after completion of radiotherapy. The median longest tumor diameter was 10 cm (range 8.2-13.6). Grade 3 toxicity and postoperative complications occurred in 3 and 4 patients, respectively. All patients showed partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST). One patient refused the operation after completion of the scheduled regimen but then had a bowel obstruction and had to undergo urgent surgery. Of the 8 patients who underwent scheduled surgery, all had R0 resection without multivisceral resection; 3 achieved pathological complete response and 5 exhibited good tumor regression. The median follow-up period was 35 months (range 9-63). Recurrences occurred in 3 of 9 patients (pelvic relapses in 2 and lung in 1). CONCLUSION: CRT/RAC appeared to be beneficial to LBURC, as it achieves remarkable rates of R0 resection, good tumor regression, and pathologic complete response. These preliminary results have to be confirmed in larger cohorts of patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Capecitabine/therapeutic use , Chemoradiotherapy/methods , Chemotherapy, Cancer, Regional Perfusion/methods , Oxaloacetates/therapeutic use , Rectal Neoplasms/therapy , Combined Modality Therapy , Digestive System Surgical Procedures , Feasibility Studies , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Bladder cancer (BC) is the fifth most common malignancy worldwide. The expression levels of microRNAs (miRNAs) in urine samples of BC patients have been demonstrated to be different from healthy people. Several studies focusing on the diagnostic value of urinary miRNAs for BC detection have been reported. The aim of this meta-analysis was to access the overall diagnostic accuracy comprehensively and quantitatively. METHODS: PubMed, Embase, Web of Science, the Cochrane Library, and CNKI were searched without language restrictions for studies about the diagnostic value of miRNAs for BC. The pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR) were calculated using the random effects model. The summary receiver operating characteristic (SROC) curve was also generated and the area under the curve (AUC) was also reckoned to assess the diagnosis accuracy. Besides, Chi-square test and I(2) test were used to assess the heterogeneity between studies. Publication bias was evaluated by the Deeks' funnel plot asymmetry test. RESULTS: Fourteen studies were included in this meta-analysis, with a total of 1,128 BC patients and 1,057 matched controls. The overall sensitivity, specificity, PLR, NLR and DOR of urinary miRNAs for the diagnosis of BC were 0.71 (95% CI: 0.67-0.75), 0.75 (95% CI: 0.70-0.79), 2.8 (95% CI: 2.3-3.4), 0.39 (95% CI: 0.33-0.46) and 7 (95% CI: 5-10), respectively. The area under the SROC curve was 0.79. Subgroup analyses suggested that the ethnicity and miRNA profiling had an obvious influence on the diagnostic accuracy. CONCLUSION: The current analysis suggested that urinary miRNA panels may be a promising noninvasive biomarker in the diagnosis of BC.
