Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value.Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT-PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc-small-nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set.Furthermore, in the expanded validation set, high expression of lnc-SNHG15 was significantly associated with lymph-node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA-SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003).Multivariate analyses demonstrated that lncRNA-SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc-SNHG15 overexpression was significantly associated with CLM and high-expression of lnc-SNHG15 in CRC was an independent predictor of poor survival. K E Y W O R D S colorectal liver metastasis, lncRNA-SHNG15, long noncoding RNA J Cell Physiol. 2019;234:7032-7039. wileyonlinelibrary.com/journal/jcp 7032 |
Abstract. Constitutive activation of TGF-β signaling pathway is a well-documented mechanism responsible for the bone metastasis of prostate cancer (PCa). MicroRNAs (miRNAs) have been reported to be crucial for the activation of TGF-β signaling via targeting downstream components of TGF-β signaling pathway. Here, we report that miR-19a-3p is downregulated in bone metastatic PCa tissues and cells. Upregulation of miR-19a-3p suppresses invasion, migration in vitro and inhibits bone metastasis in vivo in PCa cells. Conversely, silencing miR-19a-3p yields the opposite effect. Our results further demonstrate that miR-19a-3p inhibits invasion and migration abilities of PCa cells via targeting downstream effectors of TGF-β signaling, SMAD2 and SMAD4, resulting in the inactivation of TGF-β signaling. Therefore, our results uncover a novel mechanistic understanding of miR-19a-3p-induced suppressive role in bone metastasis of PCa, which will facilitate the development of effective cancer therapy methods against PCa.
Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR-874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect. Furthermore, our results demonstrated that miR-874-3p directly inhibited the expression of transcriptional co-activators YAP and TAZ of the Hippo signaling pathway, resulting in the inactivation of the TEAD transcription. Thus, our findings clarify a novel mechanism by which miR-874-3p restores chemotherapeutic sensitivity of CRC to 5-FU, indicating that offering miR-874-3p mimics in combination with 5-FU may serve as a new therapeutic strategy to circumvent the chemoresistance in CRC.
We report measurements of diamagnetic shifts for different exciton complexes confined in small InAs quantum dots. The measured diamagnetic responses are sensitive to the number of carriers in the exciton complexes, with systematic differences between neutral excitons, biexcitons, and trions. Theoretical calculations suggest that such systematic differences arise from very different extents of electron and hole wave functions confined in small quantum dots. The measured magnetic response of Coulomb energies is found to vary with the cube of the wave function extent, and can be a sensitive probe to the electron-hole wave function asymmetry.
Partial stapled hemorrhoidopexy appears to be a safe and effective technique for grade III-IV hemorrhoids. Encouragingly, PSH is associated with mild postoperative pain, few urgency episodes, and no stenosis or anal incontinence.
In the present research, tungsten oxide nanorod bundles were synthesized by a unique plasma arc gas condensation method that was both noncatalytic and template-free. W18O49 nanorod bundles were prepared by directly evaporating tungsten bulk in an oxygen-deficient environment. The as-prepared tungsten oxide nanorod bundles were characterized by FESEM, HRTEM, XRD, UV−visible spectroscopy, and PL measurements. The field-emission property was also evaluated. FESEM images showed bundlelike morphology; XRD and HRTEM results confirmed that the nanorod bundles were in a single-crystalline monoclinic W18O49 phase, with the growth direction along [010]. Also, oxygen deficiencies within the nanostructures induced the red-shift phenomenon and blue emission observed in the UV−visible and photoluminescence spectra. The field-emission measurement showed that the tungsten oxide nanorod bundles exhibited low turn-on and threshold voltages, which were about 3.5 and 4.6 V/μm, respectively. These results indicate that the tungsten oxide nanorod bundles are a promising candidate for field-emitter applications.
Older patients who are diagnosed with colon cancer face unique challenges, specifically regarding to cancer treatment. The aim of this study was to identify prognostic signatures to predicting prognosis in colon cancer patients through a detailed transcriptomic analysis. RNA-seq expression profile, miRNA expression profile, and clinical phenotype information of all the samples of TCGA colon adenocarcinoma were downloaded and differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMis) were identified. A competing endogenous RNA (ceRNA) network was constructed further and DEMs related with prognosis in the ceRNA network was screened using Cox regression analysis. Risk score models for predicting the prognosis of colon cancer patients were built using these DEMs. A total of 1476 DEMs, 9 DELs, and 243 DEMis between the tumor and normal samples were identified and functional enrichment analyses showed that the DEMs were significantly enriched in the nervous system development, ribosome biogenesis pathways in eukaryotes, and drug metabolism cytochrome P450. Twelve DEMs related with prognosis were screened from the ceRNA network. Thereafter, the risk score models of prognostic DEMs were obtained, involving seven DEMs (SGCG, CLDN23, SLC4A4, CCDC78, SLC17A7, OTOP3, and SMPDL3A). Additionally, cancer stage was identified as a prognostic clinical factor. This prognostic signature was further validated in two independent datasets. Our study developed a seven-mRNA and one-clinical factor signature that are associated with prognosis in colon cancer patients, which may serve as possible biomarkers and therapeutic targets in the future.
The 2-year recurrence rate is similar in patients with grade III-IV hemorrhoids treated with PSH or CSH. However, PSH is associated with less postoperative pain, fewer episodes of urgency, and no anal incontinence or anal stenosis.
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