Downregulation Of Transforming Growth Factor Research Articles

Long Non-Coding RNA RP1130-1 Suppresses Cell Proliferation, Invasion and Migration Mediated by Downregulation of TGF-β

Background: Hepatocellular carcinoma has low levels of long non-coding RNA (LncRNA) RP1130. However, the effects of LncRNA RP1130 in hepatocellular carcinoma still unknown. Materials and Methods: Expression of LncRNA RP1130-1 in HCC and cell lines were detected by real-time PCR. Cell proliferation was assessed by CCK-8. Wound-healing and Transwell assays were performed for HCC cell migration and invasion. Western blotting was carried out to evaluate cell cycle, migration and invasion associated proteins in HCC. Results: Expression levels of LncRNA RP1130-1 was dramatically lower in HCC tissues than in normal control. Similarly, LncRNA RP1130-1 was downregulated in HCC cell lines compared with LO2. The cellular experiments revealed that high expression of LncRNA RP1130-1 in HCC inhibited cell proliferation, migration and invasion. In addition, overexpression of LncRNA RP1130-1 inhibited the expression of transforming growth factor (TGF)-β, and TGF-β reversed the effects of LncRNA RP1130 in HCC cell lines. Conclusions: LncRNA RP1130 exerts anti-tumor effects mediated by inhibiting TGF-β. In summarize, our results indicate that LncRNA RP1130/TGFβ may be a potential therapeutic target for HCC.

TGF-\u03b2 downregulation-induced cancer cell death is finely regulated by the SAPK signaling cascade

Transforming growth factor (TGF)-β signaling is increasingly recognized as a key driver in cancer. In progressive cancer tissues, TGF-β promotes tumor formation, and its increased expression often correlates with cancer malignancy. In this study, we utilized adenoviruses expressing short hairpin RNAs against TGF-β1 and TGF-β2 to investigate the role of TGF-β downregulation in cancer cell death. We found that the downregulation of TGF-β increased the phosphorylation of several SAPKs, such as p38 and JNK. Moreover, reactive oxygen species (ROS) production was also increased by TGF-β downregulation, which triggered Akt inactivation and NOX4 increase-derived ROS in a cancer cell-type-specific manner. We also revealed the possibility of substantial gene fluctuation in response to TGF-β downregulation related to SAPKs. The expression levels of Trx and GSTM1, which encode inhibitory proteins that bind to ASK1, were reduced, likely a result of the altered translocation of Smad complex proteins rather than from ROS production. Instead, both ROS and ROS-mediated ER stress were responsible for the decrease in interactions between ASK1 and Trx or GSTM1. Through these pathways, ASK1 was activated and induced cytotoxic tumor cell death via p38/JNK activation and (or) induction of ER stress.

Effects of estrogen on lung development in a rat model of diaphragmatic hernia

Purpose The study aimed to observe the influence of estradiol on rat models with congenital diaphragmatic hernia (CDH) and understand the potential mechanism. Methods Eleven pregnant female Sprague-Dawley rats were randomly divided into 3 groups on day 9.5 of gestation: group C (n = 2) was administered 2 mL of olive oil, whereas group N (n = 3) and group E (n = 6) were administered 200 mg of nitrofen. Antenatal estradiol was given subcutaneously to group E on days 18.5, 19.5, and 20.5 of gestation. Histologic evaluations, incidence of CDH, and the immunoreactivity of transforming growth factor (TGF)- β1 in lung were observed. In addition, the mRNA levels of TGF- β1, type I TGF- β receptor (T βRI), and type II TGF- β receptor (T βRII) were determined. Results Histologically, the lungs of group N fetuses were hypoplastic compared with those of group C and had thick-walled septa with poorly developed saccules. Group E showed improved mesenchymal differentiation with well-developed saccules. There was no significant difference between the incidence of CDH in group N and that in group E. The expression of TGF- β1 in lung tissue and arterioles in group N were significantly higher than those in group C and E. Moreover, relative mRNA expression levels of TGF- β1 and T βRI in group N were markedly higher than those in group C, whereas those in group E were significantly decreased compared with group N. Conclusions Estradiol can promote lung development in rats with CDH. The down-regulation of TGF- β1 and its signaling pathway may play a role in this effect.

Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors in rat preosteoblastic RCT-1 cells.

Retinoic acid induces differentiation of preosteoblastic cells. We have demonstrated that osteoblastic differentiation and down-regulation of transforming growth factor (TGF)-beta receptors requires the interaction of type I collagen with alpha 2 beta 1 integrin (J Biol Chem 271: 3938-3944, 1996). The purpose of this study was to clarify the role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors using preosteoblastic RCT-1 cells. Retinoic acid enhanced the expression of alkaline phosphatase and type I collagen, and reduced TGF-beta receptors in these cells. Inhibiting collagen synthesis abolished these changes. Because TGF-beta inhibits osteoblastic differentiation, the changes described here may contribute to the osteoblastic differentiation by retinoic acid.