MiRNA is a class of small non-coding RNA which has an important effect on posttranscriptional gene regulation. It can regulate the expression of the target gene at the mRNA level and further influence the protein level of the target gene. We found that ULK1 may be the target gene of miR-26a-5p, and ULK1 (unc-51 like autophagy activating kinase 1) is a key component in autophagy pathway. In this study, we overexpressed miR-26a-5p by transfecting miR-26a-5p mimic into cells and simultaneously inhibited miR-26a-5p by transfecting miR-26a-5p inhibitor into cells. We demonstrated that overexpression of miR-26a-5p can reduce the expression of ULK1 and collagen I, and decrease the activation of LC3-I to LC3-II. In contrast, inhibition of miR-26a-5p can increase the expression of ULK1 and collagen I, and increase the activation of LC3-I to LC3-II. The Dual-luciferase reporter assay showed that miR-26a-5p directly acted on the 3′UTR of ULK1 and thus affected the expression of ULK1. As such, our study demonstrated that miR-26a-5p might regulate the autophagy in cardiac fibroblasts by targeting ULK1, which may have an effect on cardiac fibrosis. To our knowledge, this is the first study that shows miR-26a-5p regulates the autophagic pathway in cardiac fibroblasts.

Background: A proliferation-inducing ligand (APRIL) is a tumor-necrosis factor (TNF) family member and is a novel cytokine crucial in sustaining lymphocytic leukemia B cell survival and proliferation. However, its role in gastric cancer (GC) remains unclear. In this study, we investigated the expression pattern and prognostic role of APRIL in GC. Methods: Expression of APRIL was assessed by immunohistochemistry and real-time PCR. Prognostic role of APRIL expression was evaluated. We also discovered the effect of APRIL on chemo-resistance in GC cells and the underlying mechanisms. Results: APRIL mRNA levels were significantly increased in GC tissues compared with adjacent tissues and high expression levels of APRIL in tumor cells significantly correlated with poor overall survival in patients receiving cisplatin adjuvant treatment. Overexpression of APRIL in AGS cells significantly attenuated the therapeutic efficacy of cisplatin in vitro and in vivo. In contrast, silence of APRIL in SGC7901 cells enhanced cisplatin-induced tumor suppression. Our data further revealed that the canonical NF-κB pathway was involved in APRIL-mediated chemo-resistance. In addition, expression of APRIL was regulated by miR-145 in GC cells. Conclusion: APRIL is a novel clinical chemo-resistance biomarker for gastric cancer and might be a promising therapeutic target for GC patients.

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Long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and development of endometrial carcinoma (EC). Here, using RNA sequencing analysis, we systemically screened and identified the lncRNA eukaryotic translation initiation factor 1A, X-linked (EIF1AX)-AS1, which is aberrantly downregulated in clinical EC tissues and closely correlated with tumor type. EIF1AX-AS1 markedly inhibited EC cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, EIF1AX-AS1 interacts with EIF1AX mRNA and poly C binding protein 1 (PCBP1), which promote EIF1AX mRNA degradation. Intriguingly, by interacting with internal ribosome entry site-related protein Y-box binding protein 1 (YBX-1), EIF1AX promotes c-Myc translation through the internal ribosome entry site pathway. c-Myc promotes EIF1AX transcription and thus forms a feed-forward loop to regulate EC cell proliferation. Taken together, these data reveal new insights into the biology driving EC proliferation and highlights the potential of lncRNAs as biomarkers for prognosis and future therapeutic targets for cancer.

Background:The tricho-rhino-phalangeal syndrome-1 gene (Trps1) is an atypical GATA family member. Although current studies of Trps1 mainly focus on tumors, whether Trps1 plays a role in the male reproductive system remains unknown. Objectives:The purpose of this study was to elucidate the function of Trps1 in Leydig cells, indicating its regulatory mechanism on the cell cycle.Methods: Gene-silencing technology, RNA-seq, RT-qPCR, and western blotting were used to evaluate the function of Trps1 in mouse primary Leydig cells and MLTC-1 cells.In addition, ChIP-base sets and ChIP-qPCR were employed to further assess the regulatory mechanism of Trps1 in MLTC-1 cells. Results: Knockdown ofTrps1 in Leydig cells significantly suppressed phosphorylation of Src and Akt and expression of Ccnd1, which was accompanied by impairment of cell proliferative ability. Trps1 may affect the cell cycle through the Src/Akt/Ccnd1 signaling pathway. In addition, Trps1 may bind to the promoter of Srcin1 to regulate its transcription, thus influencing Src phosphorylation levels and the proliferation of Leydig cells. Discussion and conclusion: Src increases in Leydig cells during pubertal development, suggesting its functional involvement in differentiated adult Leydig cells. Inhibition of the Src/Akt pathway would reduce Ccnd1 expression. In the present study, we found that Trps1 may regulate the phosphorylation level of Src and Akt through Srcin1, targeting Ccnd1 to influence mouse Leydig cell proliferation. These findings shed light on the regulation of Trps1 on cell proliferation and differentiation of mouse Leydig cells.