MicroRNA-21 targets tumor suppressor genes in invasion and metastasis

MicroRNAs (miRNAs ) 是在 post-transcriptional 指向编码蛋白质的 mRNAs 的小非编码的 RNA 铺平的自然地发生的一个班。我们的以前的研究建议 mir-21 作为 oncogene 工作并且在 tumorigenesis 有一个角色，部分地通过肿瘤的规定压制或基因对流肌浆球蛋白 1 (TPM1 ) 。给那 TPM1 在房间移植被含有，在我们进一步调查了的这研究在房间侵略和肿瘤转移的 mir-21 的角色。我们发现在变形乳癌 MDA-MB-231 房间的 mir-21 的抑制显著地减少了侵略和肺转移。与这一致， TPM1 的宫外的表示显著地减少了房间侵略。而且，我们识别了二个另外的直接 mir-21 目标，规划房间死亡 4 (PDCD4 ) 并且妈大头针，哪个在侵略和转移被含有。象 TPM1 一样， PDCD4 和妈大头针也减少了 MDA-MB-231 房间的侵略海角。最后， PDCD4 的表示和妈大头针相反地在人的胸肿瘤标本与 mir-21 表示相关，显示由在这些肿瘤的 mir-21 的 PDCD4 和妈大头针的潜在的规定。总起来说，结果建议作为 oncogenic miRNA， mir-21 由指向多重肿瘤 / 转移不仅在肿瘤生长而且在侵略和肿瘤转移有一个角色压制或基因。因此， mir-21 的抑制可以为先进癌症的治疗提供一条新奇途径。

Interaction of pregnane X receptor with hypoxiainducible factor-1 regulates chemoresistance of prostate cancer cells

Aim:The nuclear pregnane X receptor(PXR)is a pivotal regulator of steroid and xenobiotics metabolism and plays an important role in shaping tumor cell responses to chemotherapy.Hypoxia within tumor tissue has multifaceted effects,including multiple drug resistance.The goal of this study was to determine whether PXR contributes to hypoxia-induced drug resistance.Methods:Metastatic prostate cancer cells were used to study the interaction of PXR and hypoxia-inducible factor-1(HIF-1 in drug resistance associated with hypoxia.The activities of PXR and HIF-1 were determined by assays for its reporter gene or target gene expression.Co-immunoprecipitation(Co-IP)was used to determine the interaction of PXR and HIF-1.Ablation or inhibition of PXR or HIF-1 was used to determine their roles in hypoxia-induced chemoresistance.Results:PXR was activated by hypoxia,leading to increased expression of multidrug resistance protein 1(MDR1).Inhibition of PXR by pharmacological compounds or depletion by shRNAs reduced the hypoxic induction of MDR1 and sensitized prostate cancer cells to chemotherapy under hypoxia.HIF-1 was required for PXR activation under hypoxia.Co-immunoprecipitation results showed that HIF-1 and PXR could physically interact with each other,leading to crosstalk between these two transcription factors.Conclusion:PXR contributes to hypoxia-induced drug resistance in prostate cancer cells through its interaction with HIF-1.