Comparative transcriptomic and metabolomic profiles reveal fruit peel color variation in two red pomegranate cultivars.

Pomegranate (Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate 'Hongbaoshi' and a purple-red-skinned cultivar 'Moshiliu', by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of 'Hongbaoshi' but high Dp in late stages of 'Moshiliu' were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of 'Moshiliu'. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in 'Moshiliu' compared with 'Hongbaoshi'. Alao, ANR was specially expressed in 'Hongbaoshi', with extremely low expression levels in 'Moshiliu'. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYBs and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin 'Moshiliu'. SG4 MYBs exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in 'Moshiliu' pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate.

A novel LINC00478 serves as a tumor suppressor in endometrial carcinoma progression.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis and progression of various cancers, but their roles in endometrial cancer (EC) are largely unknown. METHODS: The expressions of LINC00478 and PTBP1 in EC tissues were determined by RT-qPCR. Cell counting kit-8, flow cytometry and Transwell assays were executed for detecting the roles of LINC00478 in EC cells proliferation, migration and invasion. The mouse-xenograft models were established by subcutaneous injection in vivo. The interaction between LINC00478 and PTBP1 was confirmed by RNA pull-down assay and RNA-binding protein immunoprecipitation assay. RESULTS: LINC00478 was significantly down-regulated in EC tissues while compared to that in their paracancerous samples, and a higher expression level of LINC00478 was negatively correlated with clinical progress of EC patients. Functional experiments in vivo and in vitro revealed that LINC00478 overexpression could dramatically retard the proliferation of EC cells, decrease the rate of colony formation, suppress the migration and invasion abilities of EC cells in vitro and inhibit tumor growth in vivo. Mechanistically, LINC00478 regulated the expression of PTBP1, a key factor in the Warburg effect, and affected the metabolic process of EC cells. CONCLUSIONS: LINC00478 acts as a tumor suppressor in EC by negatively controlling PTBP1 expression and influencing the Warburg effect, providing a potential biomarker and therapeutic target for patients with EC.

Long non-coding RNA AGER-1 inhibits colorectal cancer progression through sponging miR-182.

OBJECTIVE: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1, has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer. METHODS: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer. RESULTS: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = -0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER, through acting as a competing endogenous RNA for miR-182 in colorectal cancer. CONCLUSION: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER, which may serve as a target for colorectal cancer diagnosis and treatment.

Analysis of Survival-Related lncRNA Landscape Identifies A Role for LINC01537 in Energy Metabolism and Lung Cancer Progression.

Many long non-coding RNAs (lncRNAs) have emerged as good biomarkers and potential therapeutic targets for various cancers. We aimed to get a detailed understanding of the lncRNA landscape that is associated with lung cancer survival. A comparative analysis between our RNA sequencing (RNA-seq) data and TCGA datasets was conducted to reveal lncRNAs with significant correlations with lung cancer survival and then the association of the most promising lncRNA was validated in a cohort of 243 lung cancer patients. Comparing RNA-seq data with TCGA ones, 84 dysregulated lncRNAs were identified in lung cancer tissues, among which 10 lncRNAs were significantly associated with lung cancer survival. LINC01537 was the most significant one (p = 2.95 × 10-6). Validation analysis confirmed the downregulation of LINC01537 in lung cancer. LINC01537 was observed to inhibit tumor growth and metastasis. It also increased cellular sensitivity to nilotinib. PDE2A (phosphodiesterase 2A) was further identified to be a target of LINC01537 and it was seen that LINC01537 promoted PDE2A expression via RNA-RNA interaction to stabilize PDE2A mRNA and thus echoed effects of PDE2A on energy metabolism including both Warburg effect and mitochondrial respiration. Other regulators of tumor energy metabolism were also affected by LINC01537. These results elucidate a suppressed role of LINC01537 in lung cancer development involving tumor metabolic reprogramming, and we believe that it might be a biomarker for cancer survival prediction and therapy.

Long Noncoding RNA PRRG4-4 Promotes Viability, Cell Cycle, Migration, and Invasion in Lung Cancer Cells.

There is a perception that long noncoding RNA (lncRNA) has relationship with carcinogenesis. Many studies have previously identified and validated that the section of chromosome 11p13 is associated with high incidence of tumor. In this study, we investigated a new lncRNA, named lncPRRG4-4, mapped to 11p13 and suspected that lncPRRG4-4 was a potential lung cancer-related gene. To explore its role in carcinogenesis, we first demonstrated that lncPRRG4-4 was upregulated in lung cancer tissues compared with adjacent nontumor tissues and functioned as an oncogene in lung cancer cells. The lncPRRG4-4 was significantly upregulated in lung cancer tissues compared with adjacent normal counterparts (mean ± standard deviation: 0.12 ± 0.84 vs. 0.05 ± 0.22; p < 0.001). Patients with metastasis exhibited high levels of lncPRRG4-4 expression than those without metastasis in both the southern samples (p = 0.045) and eastern samples (p = 0.030), total samples (p = 0.004). In addition, downregulation of lncPRRG4-4 expression inhibited lung cancer proliferation, viability, migration, and invasion ability, arrested cell cycle, facilitated apoptosis, and vice versa. Taken together, these observations suggested that the lncPRRG4-4 functions as an oncogene in lung cancer cells.

Upregulation of LncRNA FEZF-AS1 is associated with advanced clinical stages and family history of cancer in patients with NSCLC.

Antisense RNA (AS) is a type of long non-coding RNAs that functions as a post-transcriptional regulatory element on regulating parental coding gene expression via directly binding to complementary mRNA sequences. We aimed to investigate the effect of the AS to FEZF1 gene on non-small cell lung cancer (NSCLC) development. The expression level of lncRNA FEZF-AS1 and FEZF1 was determined by the quantitative Real-time PCR in 160 cases of NSCLC tissues and their adjacent non-tumour tissues. We found that lncRNA FEZF-AS1 was significantly up-regulated in tumour tissues when compared to the adjacent non-cancerous tissues (P = 0.001), and it's high expression correlated with advanced stages (P = 0.002) and Tumour Family History (P = 0.029). Meanwhile, In 58 cases of NSCLC tissues the expression of lncRNA FEZF-AS1 was positively associated with that of FEZF1expression (r = 0.8810, p = 1.6575E-20). By GEPIA database analysis, we also found that the expression of lncRNA FEZF-AS1 and FEZF1 were significantly higher in tumour tissues than those of the adjacent non-cancerous tissues in 969 NSCLC patients (P < 0.05), and lncRNA FEZF-AS1 was positively correlated with FEZF1 (r = 0.90, P < 0.001). These results suggest that lncRNA FEZF-AS1 relate to the progression of lung cancer patients and it may be a potential target for cancer therapy.