Biological Characteristics and Molecular Mechanisms of Fludioxonil Resistance in Fusarium graminearum in China.

Fusarium graminearum is the primary causal agent of Fusarium head blight (FHB) of wheat. The phenylpyrrole fungicide fludioxonil is not currently registered for the management of FHB in China. The current study assessed the fludioxonil sensitivity of a total of 53 F. graminearum isolates collected from the six most important wheat-growing provinces of China during 2018 and 2019. The baseline fludioxonil sensitivity distribution indicated that all of the isolates were sensitive, exhibiting a unimodal cure with a mean effective concentration for 50% inhibition value of 0.13 ± 0.12 µg/ml (standard deviation). Five fludioxonil-resistant mutants were subsequently induced by exposure to fludioxonil under laboratory conditions. Ten successive rounds of subculture in the absence of the selection pressure indicated that the mutation was stably inherited. However, the fludioxonil-resistant mutants were found to have reduced pathogenicity, higher glycerol accumulation, and higher osmotic sensitivity than the parental wild-type isolates, indicating that there was a fitness cost associated with fludioxonil resistance. In addition, the study also found a positive cross resistance between fludioxonil, procymidone, and iprodione, but not with other fungicides such as boscalid, carbendazim, tebuconazole, and fluazinam. Sequence analysis of four candidate target genes (FgOs1, FgOs2, FgOs4, and FgOs5) revealed that the HBXT2R mutant contained two point mutations that resulted in amino acid changes at K223T and K415R in its FgOs1 protein, and one point mutation at residue 520 of its FgOs5 protein that resulted in a premature stop codon. Similarly, the three other mutants contained point mutations that resulted in changes at the K192R, K293R, and K411R residues of the FgOs5 protein but none in the FgOs2 and FgOs4 genes. However, it is important to point out that the FgOs2 and FgOs4 expression of all the fludioxonil-resistant mutants was significantly (P < 0.05) downregulated compared with the sensitive isolates (except for the SQ1-2 isolate). It was also found that one of the resistant mutants did not have changes in any of the sequenced target genes, indicating that an alternative mechanism could also lead to fludioxonil resistance.

Long noncoding RNA PCAT6 regulates cell growth and metastasis via Wnt/ß-catenin pathway and is a prognosis marker in cervical cancer.

OBJECTIVE: Previously, long noncoding RNAs (lncRNAs) have been reported to have critical regulatory roles in the progression of human cancers. LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to act as an oncogene in several tumors. However, its expression and function in cervical cancer (CC) have not been investigated. In this study, we aim to reveal the functions of PCAT6 and the underlying mechanisms in CC. PATIENTS AND METHODS: We evaluated the expression levels of PCAT6 in CC tissues and cell lines using real-time PCR. The clinical data were interpreted by chi-square test, Kaplan-Meier survival analyses, univariate analysis, and multivariate analysis. The effect of PCAT6 on CC proliferation and metastasis was investigated by CCK-8 assay, EdU incorporation assay and transwell assay. The cell apoptosis was detected by apoptosis flow detection. RT-PCR and Western blotting were used to detect the expression levels of ß-catenin, cyclin D1 and c-myc. RESULTS: We found that PCAT6 expression was significantly up-regulated in human CC tissues and cell lines compared with their normal counterparts, and its high levels were associated with advanced FIGO stage, depth of cervical invasion and positively lymph node metastasis. Survival assays indicated that high PCAT6 expression had a negative influence on overall survival and disease-free survival. Moreover, multivariate analysis identified high PCAT6 expression as an unfavorable prognostic biomarker for CC patients. Functionally, knockdown of PCAT6 significantly suppressed CC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic investigation showed PCAT6 activates Wnt/ß-catenin signaling in CC cell lines by promoting the expression of ß-catenin, cyclin D1 and c-myc. CONCLUSIONS: Our results indicated that PCAT6 played oncogenic roles and can be used as a therapeutic target for treating human CC.

FEAT expression correlates with tumor size, PR status, HER2 expression, Ki67 index, and molecular subtype and predicts recurrence in breast cancer.

FEAT protein is uniformly overexpressed in a variety of human cancers but weakly expressed in normal tissue. FEAT has antiapoptotic activity and plays a role in carcinogenesis; however, the correlation between FEAT and clinicopathologic characteristics in cancer has not been reported. Our study explores the expression of FEAT protein and its clinicopathologic significance in breast cancer. We examined the expression of FEAT in tissues from 131 cases of breast cancer by immunohistochemistry and analyzed the correlation between FEAT expression and clinicopathologic parameters. The difference in FEAT expression between normal breast tissues and breast cancer tissues was also investigated. Finally, we analyzed the association between FEAT expression and disease-free survival or overall survival. Our data showed that FEAT was expressed in the cytoplasm. The expression of FEAT protein was significantly higher in breast cancer tissues than in normal breast tissues. Moreover, the expression of FEAT protein was higher in breast cancer with a larger tumor size (>2 cm), negative PR, positive HER2, or higher Ki67 index (≥14%) than in breast cancer with a smaller tumor size (≤2 cm), positive PR, negative HER2, or lower Ki67 index (<14%) (P<0.05). In addition, the expression of FEAT protein was associated with tumor size, PR status, HER2 expression, Ki67 index, and molecular subtype. Survival analysis showed that disease-free survival and overall survival were significantly shorter in breast cancer patients with high FEAT expression than in those with low expression of FEAT (P<0.05). COX regression analysis showed that FEAT was an independent prognostic factor for recurrence in breast cancer, but not for survival. In conclusion, FEAT may be a potential biomarker for recurrence of breast cancer.