CERS6 antisense RNA 1 promotes colon cancer via upregulating mitochondrial calcium uniporter.

BACKGROUND: Colon cancer (CC) belongs to a common cancer of digestive system. Long non-coding RNAs (lncRNAs) are dysregulated in numerous cancers and affect their development. The function of lncRNA CERS6 antisense RNA 1 (CERS6-AS1) in CC remains unclear. MATERIALS AND METHODS: CERS6-AS1 expression in colon adenocarcinoma tissues and CC cell lines was assessed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction analysis. The function of CERS6-AS1 in CC was analysed by 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling, wound healing, Transwell and immunofluorescence assays. Mechanistic analyses including RNA pull down, RNA-binding protein immunoprecipitation and luciferase reporter assay revealed the interaction between RNAs. RESULTS: CERS6-AS1 expression was aberrantly upregulated in colon adenocarcinoma tissues and CC cell lines. CERS6-AS1 knockdown inhibited CC cell malignant phenotypes and in vivo tumour growth. CERS6-AS1 served as the competing endogenous RNA of microRNA-16-5p in CC, and microRNA-16-5p inhibition partly rescued the effects of CERS6-AS1 depletion on CC development. Mitochondrial calcium uniporter was targeted by microRNA-16-5p. Mitochondrial calcium uniporter upregulation completely remedied the influence of CERS6-AS1 silencing in CC progression. Moreover, CERS6-AS1 enhanced the stability of mitochondrial calcium uniporter messenger RNA via recruiting RNA-binding protein embryonic lethal abnormal vision like 1. CONCLUSION: CERS6-AS1 promotes the development of CC via upregulating mitochondrial calcium uniporter expression.

CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis.

BACKGROUND: Circular RNAs (circRNAs) have emerged as vital regulators in human cancers, including colorectal cancer (CRC). In this study, we aimed to explore the roles of circRUNX1 in CRC. METHODS: The levels of circRUNX1, RUNX1 mRNA, solute carrier family 38 member 1 (SLC38A1) mRNA and microRNA-485-5p (miR-485-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The protein level of SLC38A1 was measured by Western blot assay. Cell colony formation, migration, invasion and apoptosis were assessed by colony formation assay, wound-healing assay, Transwell assay and flow cytometry analysis, respectively. The interaction between miR-485-5p and circRUNX1 or SLC38A1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The levels of extracellular glutamine, intracellular glutamate and α-ketoglutarate (α-KG) were measured with specific kits. The functional role of circRUNX1 in CRC development in vivo was explored by murine xenograft model assay. RESULTS: CircRUNX1 was upregulated in CRC tissues and cells compared with normal tissues and cells. CircRUNX1 deficiency restrained CRC cell colony formation, migration, invasion and glutaminolysis and induced apoptosis in vitro as well as blocked tumour growth in vivo. CircRUNX1 directly sponged miR-485-5p, which negatively modulated SLC38A1 expression in CRC cells. The effects of circRUNX1 knockdown on CRC cell colony formation, migration, invasion, apoptosis and glutaminolysis were reversed by miR-485-5p inhibition. Moreover, miR-485-5p overexpression repressed the malignant behaviours of CRC cells, with SLC38A1 elevation overturned the impacts. CONCLUSION: CircRUNX1 promoted CRC cell growth, metastasis and glutamine metabolism and repressed apoptosis by elevating SLC38A1 through sponging miR-485-5p, which might provide a novel target for CRC treatment.

LINC00667/miR-449b-5p/YY1 axis promotes cell proliferation and migration in colorectal cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been defined as vital regulators in the progression of human cancers, including colorectal cancer (CRC). Long intergenic non-protein coding RNA 667 (LINC00667) is a tumor promoter in several cancer types, while its role in CRC remains to be unmasked. This study focused on exploring the potential function and regulatory mechanism of LINC00667 in CRC. METHODS: qRT-PCR analysis was applied to detect the expression of LINC00667 in CRC cells. Loss-of function assays revealed the role of LINC00667 silencing in regulating CRC cell proliferation, apoptosis and migration. In vivo study demonstrated the effect of LINC00667 silencing on CRC cell growth. Mechanism experiments were conducted to determine the upstream or the downstream molecular mechanism of LINC00667 in CRC cells. RESULTS: LINC00667 was expressed at high level in CRC cells. LINC00667 knockdown significantly inhibited CRC cell growth and migration. YY1 transcription factor induced the upregulation of LINC00667 in CRC cells by transcriptionally activating LINC00667. In addition, miR-449b-5p could interact with LINC00667 in CRC cells. Intriguingly, miR-449b-5p directly targeted to YY1, thus inhibiting YY1 expression. YY1 recovered the CRC cell functions impaired by LINC00667 silencing. CONCLUSIONS: LINC00667 is transcriptionally activated by YY1 and promotes cell proliferation and migration in CRC by sponging miR-449b-5p to upregulate YY1.

[Analysis of effect of screening of esophageal cancer in 12 cities and counties of Henan province].

OBJECTIVE: To evaluate effect of screening of esophageal cancer at rural areas in Henan province. METHODS: At rural areas with high incidence of upper gastrointestinal carcinoma in Henan province total of 88,263 persons with 40 to 69 years old were set to the target population of the screening by the 12 cities and countries and endoscope and pathology diagnosis were performed during 2009-2013. For patients with precancerous lesions, follow-up visits were conducted and defined as follows: once in three years for patients with mild dysplasia, once per year for moderate hyperplasia patients, the patients with severe intraepithelial neoplasia/carcinoma in situ should be treat, at least once per year for those one who didn't under treatment. The result data of screening were summarized and detection rates of esophagus hyperplasia, carcinoma in situ, early and middle-late cancer were calculated, as well as the early diagnosis rate. The result between first round and follow-up screening was compared. RESULTS: Target population were examined in first round screening. There were 8,434 persons with above mild dysplasia and the detection rate was 9.56%, among them there were 7,224 (8.18%) cases with light-middle hyperplasia, 789 (0.89%) cases with serious dysplasia or cancer in situ, 239 (0.27%) cases with early cancer and 182 (0.21%) cases with middle-late cancer. The sum of serious dysplasia or cancer in situ and early cancer was 1 028 and the early detection rate was 84.96% (1,028/1,210). From 2012 to 2013, the follow-up screening for persons with light-middle hyperplasia which should be followed 4,230 cases, there were 2 853 people to take in screening and compliance was 67.45%. Total of 94 cases were diagnosed with cancer in situ or early cancer. The detection rate and the early detection rate were 3.29% and 100%, respectively. The rates of detection and early detection in phase of follow-up screening were statistically significantly higher than that in first round screening respectively (P<0.001). CONCLUSION: At rural areas of high incidence upper gastrointestinal carcinoma in Henan province, the screening with endoscope had good effect and strengthening the follow-up screening could increase the effect.

[Analysis of results of endoscopic screening of esophageal, gastric cardia and gastric cancers in high risk population].

OBJECTIVE: To summarize the results of endoscopic screening of esophageal, gastric cardiac and gastric cancers in the high-risk population, and analyze the influencing factors such as age, gender and biopsy rate on their detection and early diagnosis rates. METHODS: Nine high incidence cities and counties of esophageal cancer in Henan province were included in this study. People aged 40-69 years were set to the target population. Excluding contraindications for gastroscopy, in accordance with the national technical scheme of early cancer diagnosis and treatment, gastroscopic screening and biopsy pathology for human esophageal, cardiac and gastric cancers were carried out. RESULTS: During the 3-year period, a total of 40 156 subjects were screened. Among them, 18 459 cases of various precancerous lesions (46.0%) were detected. The cancer detection rate was 2.3% (916 cases), including 763 cases of early cancers. The diagnosis rate of early cancers was 83.3%. Precancerous lesions were detected in 9297 cases (23.2%) for esophagus and 9162 cases (22.8%) for gastric cardia as well as stomach, respectively. CONCLUSIONS: The results of this study demonstrate that endoscopic screening is feasible for early detection, diagnosis and treatment of esophageal, gastric cardia and gastric cancers among high risk population in high incidence area. Exploration analysis of relevant affecting factors may help to further improve the screening project for early diagnosis and treatment of those cancers.

Esophageal/gastric cancer screening in high-risk populations in Henan Province, China.

OBJECTIVE: To summarize the endoscopic screening findings in high-risk population of esophageal and gastric carcinoma and analyze influential factors related to screening. METHODS: In seven selected cities and counties with high incidences of esophageal carcinoma, people at age of 40-69 were set as the target population. Those with gastroscopy contradictions were excluded, and all who were voluntary and willing to comply with the medical requirements were subjected to endoscopic screening and histological examination for esophageal, gastric cardia and gastric carcinoma in accordance with national technical manual for early detection and treatment of cancer. RESULTS: In three years, 36,154 people were screened, and 16,847 (46.60%) cases were found to have precancerous lesions. A total of 875 cases were found to have cancers (2.42%), and among them 739 cases had early stage with an early diagnosis rate is 84.5%. Some 715 patients underwent prompt treatment and the success rate was 81.8%. CONCLUSIONS: In a high-risk population of esophageal and gastric carcinoma, it is feasible to implement early detection and treatment by endoscopic screening. Screening can identify potential invasive carcinoma, early stage carcinoma and precancerous lesions, improving efficacy through early detection and treatment. The exploratory analysis of related influential factors will help broad implementation of early detection and treatment for esophageal and gastric carcinoma.