In addition to extracellular ligands that sig nal through membrane receptors, the chemotherapy induced DNA damage also activates NF B in some cell contexts. Many potent anti apoptosis genes are transactivated by NF B. Therefore, the activation of NF B may desensitize cells to apoptosis and thereby pro mote cancer http://www.selleckchem.com/products/CP-690550.html progression. Unfortunately, abnormal activa tion of the NF B pathway is a common phenomenon in cancer cells. MicroRNAs are evolutionarily Inhibitors,Modulators,Libraries conserved small non coding RNAs that suppress protein expression by binding to the 3 untranslated region of tar get mRNA. Several miRNAs have been reported to mod ify cell behavior by regulating the NF B pathway. For example, miR 301a, miR 30e and miR 182 promote NF B activity and thereby enhance tumor growth, inva siveness or angiogenesis.
On the contrary, miR 15 16195 and miR 146ab have been shown to impair NF B activity, thus reducing the proliferation and metastasis of tumor cells. Very few miRNAs have been char acterized to affect chemosensitivity by regulating the NF B pathway miR 143 sensitizes colorectal Inhibitors,Modulators,Libraries cancer cells to 5 fluorouracil treatment by downregulating ERK5, Bcl 2 and p65 expression miR 146a enhances the chemo sensitivity of NKT cell lymphoma to etoposide by target ing TRAF6. Clearly, identification of miRNAs that target NF B signaling may provide novel molecular tar gets for cancer therapy. It is reported that NF B signaling is frequently acti vated Inhibitors,Modulators,Libraries in hepatocellular carcinoma. In order to uncover the HCC associated miRNAs which may regulate the NF B pathway, we predicted the targets of those deregulated miRNAs that we found in HCC tis sues, using target prediction algorithms.
Among the miRNAs that were predicted to target the regulators of NF B pathway, miR 26b stood out as a potential candidate, with TAK1 and TAB3 as its puta tive targets. Studies from Inhibitors,Modulators,Libraries us and other groups show that the miR 26 family is frequently downregu lated in multiple types of cancer, including HCC, breast cancer, nasopharyngeal carcinoma and melanoma. To date, there is no report disclosing the regulatory role of miR 26ab on the NF B pathway and its biological sig nificance. Because of the share of common seed sequences for target recognition, members of a miRNA family usu ally play similar, if not identical, roles. Therefore, we ex plored the impact of miR 26b on NF B signaling and its biological significance.
We found that miR 26b suppressed the TNF and doxorubicin activated NF B signaling in HCC cells, and sensitized cancer cells to the doxorubicin induced apoptosis by targeting TAK1 and TAB3. Results miR 26b suppresses the TNF induced NF B signaling in HCC cells To explore the impact of miR 26b on NF B signaling, Inhibitors,Modulators,Libraries miR 26b or its negative control duplex was co transfected with the luciferase reporter that contained multiple NF B binding sites in its selleck chem Ruxolitinib promoter.