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Abstract Heterogeneous nuclear ribonucleoproteins (hnRNPs), a group of proteins that control gene expression, have been implicated in many post-transcriptional processes. SYNCRIP (also known as hnRNP Q), a subtype of hnRNPs, has been reported to be involved in mRNA splicing and translation. In addition, the deregulation of SYNCRIP was found in colorectal cancer (CRC). However, the role of SYNCRIP in regulating CRC growth remains largely unknown. Here, we found that SYNCRIP was highly expressed in colorectal cancer by analyzing TCGA and GEPIA database. Furthermore, we confirmed the expression of SYNCRIP expression in CRC tumor and CRC cell lines. Functionally, SYNCRIP depletion using shRNA in CRC cell lines (SW480 and HCT 116) resulted in increased caspase3/7 activity and decreased cell proliferation, as well as migration. Meanwhile, overexpression of SYNCRIP showed opposite results. Mechanistically, SYNCRIP regulated the expression of DNA methyltransferases (DNMT) 3A, but not DNMT1 or DNMT3B, which affected the expression of tumor suppressor, p16. More importantly, our in vivo experiments showed that SYNCRIP depletion significantly inhibited colorectal tumor growth. Taken all together, our results suggest SYNCRIP as a potent therapeutic target in colorectal cancer.

Abstract Background By complexing poly (ADP-ribose) (PAR) in reaction to broke strand, PAR polymerase1 (PARP1) acts as the key enzyme participated in DNA repair. However, recent studies suggest that unrepaired DNA breaks results in persistent PARP1 activation, which leads to a progressively reduce in hexokinase1 (HK1) activity and cell death. PARP-1 is TCF-4/β-A novel co activator of gene transactivation induced by catenin may play a role in the development of colorectal cancer. The molecular mechanism of PARP1 remains elusive. Methods 212 colorectal cancer (CRC) patients who had the operation at our hospital were recruited. PARP1 expression was evaluated by immunohistochemistry. Stable CRC cell lines with low or high PARP1 expression were constructed. Survival analysis was computed based on PARP1 expression. The cell proliferation was tested by CCK-8 and Colony formation assay. The interaction of PARP1 and XRCC2 was detected by immunoprecipitation (IP) analysis. Results Compared with matching adjacent noncancerous tissue, PARP1 was upregulated in CRC tissue which was correlated with the degree of differentiation, TNM stage, depth of invasion, metastasis, and survival. In addition, after constructing CRC stable cell lines with abnormal expression of PARP1, we found that overexpression of PARP1 promoted proliferation, and demonstrated the interaction between PARP1 and XRCC2 in CRC cells through immunoprecipitation (IP) analysis. Moreover, the inhibitor of XRCC2 can suppress the in vitro proliferation arousing by upregulation of PARP1. Conclusions PARP1 was upregulated in CRC cells and promoted cell proliferation. Furthermore, the expression status of PARP1 was significantly correlated with some clinicopathological features and 5-year survival.

Abstract Background Peach bacterial shot hole, caused by Xanthomonas arboricola pv pruni (Xap), is a global bacterial disease that poses a threat to the yield and quality of cultivated peach trees (Prunus persica). Results This study compared the mRNA and miRNA profiles of two peach varieties, ‘Yanbao’ (resistant) and ‘Yingzui’ (susceptible), after inoculation with Xap to identify miRNAs and target genes associated with peach tree resistance. mRNA sequencing results revealed that in the S0-vs-S3 comparison group, 1574 genes were upregulated and 3975 genes were downregulated. In the R0-vs-R3 comparison group, 1575 genes were upregulated and 3726 genes were downregulated. Through miRNA sequencing, a total of 112 known miRNAs belonging to 70 miRNA families and 111 new miRNAs were identified. Notably, some miRNAs were exclusively expressed in either resistant or susceptible varieties. Additionally, 59 miRNAs were downregulated and 69 miRNAs were upregulated in the R0-vs-R3 comparison group, while 46 miRNAs were downregulated and 52 miRNAs were upregulated in the S0-vs-S3 comparison group. Joint analysis of mRNA and miRNA identified 79 relationship pairs in the S0-vs-S3 comparison group, consisting of 48 miRNAs and 51 target genes. In the R0-vs-R3 comparison group, there were 58 relationship pairs, comprising 28 miRNAs and 20 target genes. Several target genes related to resistance, such as SPL6, TIFY6B, and Prupe.4G041800_v2.0.a1 (PPO), were identified through literature reports and GO/KEGG enrichment analysis. Conclusion In conclusion, this study discovered several candidate genes involved in peach tree resistance by analyzing differential expression of mRNA and miRNA. These findings provide valuable insights into the mechanisms underlying resistance to Xap in peach trees.

Abstract To explore the relationship between miR-373 and the occurrence and development of colorectal cancer. Additionally, it aims to predict the potential cellular signaling pathways and regulatory mechanisms in which miR-373 may be involved and provides a theoretical basis and experimental evidence for the clinical application of miR-373 as a potential biomarker, molecular target, and prognostic indicator in colorectal cancer. Real-time quantitative PCR is used to analyze the expression of miR-373 in human colorectal cancer cell lines and normal human colonic epithelial cells. Further validation of the differential expression of miR-373 in colorectal cancer cell lines is being performed. Biological functions such as cell proliferation, invasion and apoptosis are being detected by MTT, CCK-8, transwell, cell cycle analysis, and flow cytometry experiments to verify the changes in the biological behavior of colon cancer cells after overexpression and interference of miR-373 in SW-480 cells and to explore the effects of miR-373 on cell proliferation, invasion, and apoptosis in colon cancer cells. Proteomic analysis is being conducted on proteins extracted from miR-373 overexpressing SW480 cells, and mass spectrometry is used for protein identification. GO, KEGG, and enrichment analysis are being employed to analyze the significantly differentially expressed proteins. The expression levels of pathway-related proteins are being verified using Western blot. Overexpression of miR-373 increased the invasive and metastatic ability of SW-480 cells; knockdown of miR-373 decreased the invasive and metastatic ability of SW-480 cells. However, there was no statistically significant effect on cell proliferation and apoptosis in SW-480 cells. Proteomic analysis identified 78 differentially expressed proteins based on fold change (FC) > 1.2 and P

Summary: Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a key target, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFβ1 expression and activates the TGFβ1/Smad2 pathway, which not only promotes EMT development but also induces VEGF-C secretion and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor in lymphatic metastasis and suggest that HOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.