TGF-ß1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression.

Transforming growth factor-ß1 (TGF-ß1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-ß1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-ß1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-ß1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-ß1 contributes to the progression of PCa.

Bone Marrow Mesenchymal Stem Cells Ameliorate Cisplatin-Induced Renal Fibrosis via miR-146a-5p/Tfdp2 Axis in Renal Tubular Epithelial Cells.

Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury (AKI). However, the potential function of MSCs in chronic kidney disease remains elusive. Renal fibrosis is the common endpoint of chronic progressive kidney diseases and causes a considerable health burden worldwide. In this study, the protective effects of bone marrow mesenchymal stem cells (BM-MSCs) were assessed in repeated administration of low-dose cisplatin-induced renal fibrosis mouse model in vivo as well as a TGF-ß1-induced fibrotic model in vitro. Differentially expressed miRNAs in mouse renal tubular epithelial cells (mRTECs) regulated by BM-MSCs were screened by high-throughput sequencing. We found microRNA (miR)-146a-5p was the most significant up-regulated miRNA in mRTECs. In addition, the gene Tfdp2 was identified as one target gene of miR-146a-5p by bioinformatics analysis. The expression of Tfdp2 in the treatment of BM-MSCs on cisplatin-induced renal injury was evaluated by immunohistochemistry analysis. Our results indicate that BM-MSC attenuates cisplatin-induced renal fibrosis by regulating the miR-146a-5p/Tfdp2 axis in mRTECs.

Anatomical study of the communicating branches of cords of the brachial plexus and their clinical implications.

The aim of this study was to investigate the occurrence and patterns of the communicating branches of cords of the brachial plexus (BPs). This study was performed with 50 fixed adult cadavers (all 100 sides). The BPs were exposed, the presence of the communicating branches of BPs were determined, measured, and photographed. The communicating branches were identified in 27 sides of the BPs. According to enthesis, the communicating branches between the medial and lateral cords (25 sides) were divided into five types. The most common branches connected the lateral cord with the medial root of the median nerve (16 sides). All the communicating branches between the lateral and medial cords obliquely crossed anterior to the axillary artery and passed below the thoracoacromial artery trunk. The distance of the communicating branch with the origin of thoracoacromial artery trunk was 1.60 ± 0.64 cm. The length, transverse diameter, and anteroposterior diameter of communicating branch were 1.67 ± 0.62 cm, 1.77 ± 0.63 mm, and 1.91 ± 0.34 mm, respectively. These anatomical data about the communicating branches will be helpful for surgeons who perform surgical procedures in the cervical and axillary regions.

Anatomical study and clinical significance of the rami communicantes between cervicothoracic ganglion and brachial plexus.

The aim of this study was to provide a detailed characterization of the rami communicantes between the stellate (or cervicothoraic) ganglion (CTG) and brachial plexus (BP). Rami communicantes of 33 fixed adult cadavers were macroscopically observed, and connection between CTG and spinal nerves and branching was investigated. In all cases, except one, the hibateral medial rami communicantes was found to be positioned symmetrically between the CTG and C7, C8 spinal nerves. Gray rami communicantes arising from the CTG joined C8, C7, C6 nerve roots on 66, 63, and 6 sides, respectively, and branched from the rami communicantes to C7, C6, C5 nerve roots lying on 51, 41, and 2 sides, respectively. Forty-five sides of the branches from rami communicantes derived from CTG to C8 were observed to ascend through the transverse foramina of the C7 nerve. The branches from rami communicantes derived from CTG to C7 to the C6 nerve were observed ascending through the foramen transversarium of the six cervical vertebrae along with the vertebral artery and joining the C6 spinal nerve in 41 sides. Knowledge about the general distribution and individual variations of the rami communicantes between CTG and BP will be useful toward studies involving the inference of sympathetic nerve stimulation of the upper limbs and could be important for surgeons who perform surgical procedures in the cervical region or medical blockade of nerve fibers.

Expression of E-cadherin and nm23 is associated with the clinicopathological factors of human non-small cell lung cancer in China.

E-cadherin, a calcium-dependent cell-cell adhesion molecule, functions as maintenance of epithelial integrity. nm23, encoded by non-metastatic 23 gene, plays a key role in differentiation of many kinds of epithelium. Loss or dysfunction of E-cadherin and nm23 was frequently identified in many types of human cancers and is considered to correlate with invasive/metastatic phenotype. We previously reported that defective expression of E-cadherin might play a role in the development of the malignant phenotype in non-small cell lung cancer (NSCLC) [Q.Y. Fei, H.T. Zhang, X.F. Chen, et al., Defected expression of Ecadherin in non-small cell lung cancer, Lung Cancer 37 (2002) 147-152]. In an attempt to evaluate the significance of E-cadherin and nm23 in human non-small cell lung cancer, we performed mRNA expression and genetic structure analyses of the E-cadherin and nm23 genes in 54 NSCLCs and 46 normal lung tissues. The mRNA expression was determined by semi-quantitative RT-PCR, and genetic structure was examined through PCR-SSCP followed by sequencing. Although no mutation of the E-cadherin and nm23 genes was detected, the results obtained in the present study showed that reduction of E-cadherin and nm23 mRNA expression remarkably correlated with low histological differentiation, increasing stage as well as lymph node metastases (P<0.05). These data provide us with support for the idea that dysfunction of E-cadherin and nm23 has a role in progression of NSCLC and that the examination of E-cadherin and nm23 expression can provide experimental evidence for clinical treatment.