Grain chalkiness reduces the quality of rice (Oryza sativa) and is a highly undesirable trait for breeding and marketing. However, the underlying molecular cause of chalkiness remains largely unknown. Here, we cloned the F-box gene WCR1 (WHITE-CORE RATE 1), which negatively regulates grain chalkiness and improves grain quality in rice. A functional A/G variation in the promoter region of WCR1 generates the alleles WCR1A and WCR1G, which originated from tropical japonica (TrJ) and wild rice O. rufipogon, respectively. OsDOF17 is a transcriptional activator that binds to the AAAAG cis-element in the WCR1A promoter. WCR1 positively affects the transcription of the metallothionein gene MT2b and interacts with MT2b to inhibit its 26S proteasome-mediated degradation, leading to decreased reactive oxygen species production and delayed programmed cell death in rice endosperm. This, in turn, leads to reduced chalkiness. Our findings uncover a molecular mechanism underlying rice chalkiness and identify the promising natural variant WCR1A, with application potential for rice breeding.

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Background Actual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported. Objective This study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC. Methods We performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan–Meier analysis, and multivariate Cox proportional hazards model for the analyses. Results We included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P<.001), mucinous (HR 0.454, P<.001), and clear cell (HR 0.563, P<.001) subtypes showed better ovarian cancer-specific survival than those with the serous subtype. Similar results were found regarding overall survival. However, ovarian cancer–specific survival and overall survival were comparable among those with endometrioid, clear cell, and mucinous tumors. Conclusions Ovarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.

Background Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. Methods CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial–mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. Results CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001). Inhibiting the level of CHD1L significantly decreased cell migration and invasion (P < 0.05), increased the expression of epithelial markers, and decreased the expression of mesenchymal markers. Following inhibition of CHD1L expression, RNA-seq was conducted and 82 circRNAs had significantly upregulated expression, while 247 had significantly downregulated expression. The circRNAs were validated by PCR, and hsa_circ_0008305 (circ-PTK2) was selected and further validated by Sanger sequencing, FISH, and RT-qPCR. Circ-PTK2 expression was significantly higher in the ovarian cancer tissues compared with normal ovary tissues (P < 0.001). By regulating the level of circ-PTK2 with siRNA and an overexpression vector, expression of circ-PTK2 was found to be positively correlated to cell migration and invasion. Overexpression of circ-PTK2 enhanced tumor formation and was correlated to expression of EMT pathway markers. Prediction of the target of circ-PTK2 was validated with dual luciferase assay and identified miR-639 and FOXC1 as the valid target of circ-PTK2 and miR-639, respectively. The RNA level of miR-639 was negatively correlated to cell proliferation and migration, whereas the mRNA level of FOXC1 was positively correlated to those processes. miR-639 mimics reversed the function of circ-PTK2 overexpression; however, interference of FOXC1 mRNA also reversed the function of circ-PTK2. Conclusions circ-PTK2 is an important molecule in regulating the pathogenic processes of ovarian cancer via the miR-639 and FOXC1 regulatory cascade.