MIR31HG regulates the proliferation, migration and invasion of breast cancer by regulating the expression of POLDIP2.

PURPOSE: This study aimed to explore the role of MIR31HG and its molecular mechanism in breast cancer (BC). METHODS: The levels of MIR31HG in BC tissues and cell lines were detected. The correlations of MIR31HG expression level with clinical characteristics and prognosis of patients were analyzed. Then we detected the effects of MIR31HG on the proliferative, migrative and invasive abilities of BC cells. Subsequently, we detected the level of the predicted target POLDIP2 in BC. Furthermore, the effect of POLDIP2 on the malignant phenotype of MIR31HG-mediated BC was evaluated through recovery experiments. RESULTS: MIR31HG was aberrantly up-regulated in BC tissues and cell lines, and its level was in correlation with the patient's tumor diameter, tumor node metastasis (TNM) stage, lymph node metastasis as well as the overall survival rate. Besides, MIR31HG knockdown was able to inhibit the proliferative ability, migration and invasion of BC cells. Besides, POLDIP2 was aberrantly up-regulated in BC tissues, and its expression level was in positive correlation with the level of MIR31HG. Besides, POLDIP2 overexpression could partially inhibit the proliferative, migrative and invasive abilities of BC cells. Long non-coding (lnc)RNA MIR31HG was aberrantly up-regulated in BC and its expression was associated with poor prognosis of BC patients. Additionally, the levels of MIR31HG and POLDIP2 were positively correlated. CONCLUSIONS: The low expression of MIR31HG or POLDIP2 can inhibit the proliferative, migrative and invasive abilities of BC cells, which provides a new target for the diagnosis along with the treatment of BC.

CLK2 promotes occurrence and development of non-small cell lung cancer.

PURPOSE: To explore the role of CDC-like kinase 2 (CLK2) in the development and progression of lung cancer and its regulatory mechanism. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was used to detect the expressions of micro ribonucleic acid (miR)-573 and CLK2 in non-small cell lung cancer (NSCLC) cell lines or tissues. The cell proliferative ability after overexpression of CLK2 was determined via cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays. It was verified using dual-luciferase reporter assay and gain-loss assay that CLK2 was the target gene of miR-573, which was regulated by miR-573. According to the reverse assay, the effect of CLK2 on the proliferation of NSCLC cells was regulated by miR-573. RESULTS: In qRT-PCR, the expression of CLK2 in NSCLC tissues and cell lines significantly rose. The CLK2 expression was increased in patients with stage Ⅲ-Ⅳ NSCLC and metastasis. According to survival analysis, highly-expressed CLK2 indicated a worse prognosis. The receiver operating characteristic (ROC) curves showed that CLK2 possessed the potential as a biomarker. It was found using the bioinformatics prediction that CLK2 was a potential target of miR-573. The results of dual-luciferase reporter assay confirmed that there was a binding relation between the two, and up-regulation of miR-573 could obviously inhibit the expression of CLK2. In qRT-PCR, the miR-573 expression in lung cancer tissues obviously declined, which was significantly negatively correlated with the expression of CLK2. CCK-8 and EdU assays manifested that the proliferation of lung cancer cells could be markedly enhanced through up-regulating CLK2. Finally, the results of reverse assay showed that up-regulating miR-573 could partially reverse the promoting effect of CLK2 on cell proliferation. CONCLUSIONS: Highly-expressed CLK2 significantly enhances the proliferation of lung cancer cells, thereby promoting the occurrence and development of lung cancer, which may be regulated by miR-573.

miR­576­3p overexpression enhances cisplatin sensitivity of ovarian cancer cells by dysregulating PD­L1 and cyclin D1.

Cisplatin (DDP) resistance is a major obstacle in the chemotherapeutic efficacy of ovarian cancer. The present study aimed to explore the role of miR­576­3p in DDP sensitivity of ovarian cancer cells. Ovarian cancer cell lines SKOV3 and A2780 and DDP­resistant ovarian cancer cell lines SKOV3/DDP and A2780/DDP were used in the present study. In vitro studies demonstrated that microRNA (miR)­576­3p overexpression increased the DDP sensitivity of DDP­resistant ovarian cancer cells. A dual­luciferase assay verified that both programmed death­ligand 1 (PD­L1) and cyclin D1 were targets of miR­276­3p and were reversely associated with the expression of miR­576­3p. Moreover, in vivo studies indicated that tumorigenesis was inhibited by DDP, which was enhanced by further miR­576­3p overexpression in tumor tissues. Taken together, the results suggested that miR­576­3p overexpression increased DDP chemosensitivity of ovarian cancer cells via decreasing PD­L1 and cyclin D1, indicating that miR­576­3p may serve as a promising therapeutic target for ovarian cancer.

MicroRNA-139 Suppresses the Tumorigenicity of Triple Negative Breast Cancer Cells by Targeting SOX8.

PURPOSE: The effects of miR-139 on the tumorigenicity of triple negative breast cancer (TNBC) and the underlying mechanisms were investigated. METHODS: Normal human breast epithelial (MCF-10A) and TNBC cell lines (HCC1806 and BT549) were used for microRNA (miR)-139 overexpression, SOX8 overexpression, and knockdown studies as in vitro models of TNBC. The expression of SOX8 and miR-139 was detected by reverse transcription-polymerase chain reaction. CCK8 and clone formation assays were used to evaluate cell proliferation ability. Transwell assays and flow cytometry were used to test cell migration and apoptosis, respectively. Cell tumorigenicity was examined by tumor sphere formation assays. The interaction between miR-139 and SOX8 was examined by dual-luciferase reporter assays. The expression of SOX8, cleaved caspase-3, and cleaved caspase-9 was analyzed by Western blotting. The findings were validated in vivo using a nude mouse transplanted tumor model. RESULTS: SOX8 expression was higher (P < 0.05) and miR-139 expression was lower (P < 0.05) in HCC1806 and BT549 cells than in MCF-10A cells. SOX8 overexpression significantly enhanced cell proliferation and migration, reduced the rate of cell apoptosis, and increased tumor sphere formation (P < 0.05) compared with the control group, whereas SOX8 knockdown had the opposite effect (P < 0.05). Overexpression of miR-139 markedly decreased cell proliferation and migration, increased cell apoptosis in vitro, and decreased tumor angiogenesis and volume in vivo (P < 0.05). CONCLUSION: miR-139 suppressed the tumorigenicity of TNBC cells by targeting SOX8.

Expression of Cytosolic Phospholipase A2 (cPLA2)-Arachidonic Acid (AA)-Cyclooxygenase-2 (COX-2) Pathway Factors in Lung Cancer Patients and Its Implication in Lung Cancer Early Detection and Prognosis.

BACKGROUND The aim of this study was to elucidate the involvement of cPLA2-AA-COX-2 pathway factors and their potential role in lung cancer early diagnosis and prognosis. MATERIAL AND METHODS We selected 80 lung cancer patients as the cancer group, and 30 normal patients were selected as the normal group. Serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 were measured, and mRNA levels of COX-2, cPLA2, COX-1, and mPGES in serum were determined. Spearman's P-test was used to analyze the correlation between expression of PGI2 and mPGES in serum and the clinical characteristics of these lung cancer patients. The factors affecting the prognosis lung cancer were analyzed by COX regression model. RESULTS The serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 in the cancer patient group were significantly higher (p<0.05) than in the normal group; after treatment, the serum contents of these factors were significantly decreased (p<0.05). However, distant metastasis had a significant effect on serum contents of mPGES and PGI2 (p<0.05), but not on the other factors. The mRNA levels of COX-2, cPLA2, COX-1, and mPGES in cancer patients were significantly higher than in normal patients. In addition, the 5-year survival rate of patients with high expression of mPGES and/or PGI2 was lower than that of the low expression group. Cox regression analysis showed that the expression of mPGES and PGI2 had statistical significance in predicting the prognosis of lung cancer. CONCLUSIONS The cPLA2-AA-COX-2 pathway is closely associated with lung cancer. These findings are important for clinical diagnosis of lung cancer.

[Improved effect of comprehensive nutritional intervention of whole covering for Kazak's pregnant women, lactating women and infants in Altay farming and stockbreeding region].

OBJECTIVE: To study the effect of nutritional intervention for Kazak's pregnant women, lactating women and infants in farming and stockbreeding region of Jeminay County, Altay City. METHODS: 24 h record method was conducted to implement dietary survey, and results were used to analyze dietary structure and nutrient intake level of pregnant women, lactating women and infants. Pregnant women, lactating women and infants over 6 months were intervened with iron fortified soy sauce nutrients supplement and Yingyangbao(YYB) for 2. 4 years. Hemoglobin was detected for pregnant women, lactating women and infants by using HemoCue analyzer. RESULTS: The nutrient intakes of the pregnant women, lactating women and infants were averagely lower than that of the recommended levels. In these infants who received breast feeding, the least acceptability diet quality rate was 42. 1%, and in other infants who didn't receive breast feeding, the rate was 25%. After intervention, anemia prevalence of pregnant women, lactating women and infants were significantly reduced compared with the base line levels at 2 survey time points(2014:pregnant women χ~2=26. 27, lactating women χ~2=18. 06, infants χ~2=44. 46, 2015:pregnant women χ~2=35. 62, lactating women χ~2=25. 05, infants χ~2=39. 61;all P<0. 001). CONCLUSION: The nutrition intervention of whole covering could improve nutrition status of Kazak's pregnant women, lactating women and infants.

Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and remains a major public health issue. Therefore, further investigation is required to delineate the cellular and molecular mechanisms underlying colorectal tumorigenesis. Using CRC data taken from The Cancer Genome Atlas, we determined that the expression of otopetrin 2 (OTOP2) is highly correlated with malignancy grade and rate of patient survival. Here, we report that OTOP2 is down-regulated in cancerous tissues and that elevated OTOP2 effectively suppresses tumor proliferation in vitro. We demonstrate that wild-type p53 (wtp53), but not mutant p53 (mtp53), can regulate the transcription of otop2 in CRC cells. Subsequently, we investigate the chromatin architecture of the otop2 promoter, whereby we discover alterations in p53-dependent DNA loop organization and CCCTC-binding factor (CTCF) binding between cells with wtp53 and mtp53. In conclusion, our study promotes an in-depth understanding of tumorigenesis, which may also lead to the development of therapeutic applications targeting human malignancy.

Inhibition of PLA2G4A Reduces the Expression of Lung Cancer-Related Cytokines.

Phospholipase A2-IVA (PLA2G4A) is the most abundant subtype of cytoplasmic phospholipase A2 (cPLA2) and is an important enzyme in tumor development. Our study aimed to explore the role of PLA2G4A in the regulation of lung cancer. The contents of cell-related cytokines (microsomal prostaglandin E synthase-1 [mPGES], PGE2, and prostacyclin [PGI2]) in A549 cells were analyzed by ELISA kits. Cell counting kit-8 (CCK8) was used to detect the effects of inhibitor of cPLA2 (arachidonyl trifluoromethyl ketone [AACOCF3]) on the proliferation of A549 cells. The migration and invasion of A549 cells were tested by cell scratch wound healing assay and transwell assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the effect of inhibitor AACOCF3 on the expression of related mRNA and protein in A549 cells. ELISA result showed that the levels of mPGES, PGE2, and PGI2 in control group were significantly higher than those in the AACOCF3 group. Cell inhibition rate in the control group was significantly lower than that in the AACOCF3 group. The percentage of wound healing in the control group was significantly higher than that in the AACOCF3 group. Meanwhile, the relative invasive number of cells in the control group was significantly higher than those in the AACOCF3 group. The expression levels of related mRNA of PLA2G4A and cyclooxygenase-2 (COX-2) and the expression levels of mPGES, COX-1, and COX-2 protein in the control group were significantly higher than those in the AACOCF3 group. Our research showed that PLA2G4A was involved in migration and invasion of lung cancer cells.