ABSTRACT
Dysregulated expression of microRNAs (miRNAs) has been observed in numerous types of human cancer, including cervical cancer (CC). The present study aimed to elucidate the expression and roles of miR181 in cervical cancer tissues and cells. HeLa cells with a stable overexpression of miR181 were generated and injected subcutaneously into the front legs of nude mice. Functional assays revealed a reduced rate of proliferation and an enhanced rate of apoptosis following transfection of CC cells with miR181 mimics. In addition, miR181 also suppressed tumor growth in the nude mice. At the molecular level, it was found that Yin Yang 1, an oncogene in several types of human cancer, was negatively regulated by miR181. Therefore, the findings of the present study suggest that exogenous overexpression of miR181 may be a potential approach for the treatment of CC in the future.
Subject(s)
MicroRNAs/metabolism , Uterine Cervical Neoplasms/pathology , YY1 Transcription Factor/metabolism , 3' Untranslated Regions , Animals , Base Sequence , Cell Proliferation/drug effects , Disease Progression , Down-Regulation/drug effects , Female , G1 Phase Cell Cycle Checkpoints/drug effects , HeLa Cells , Humans , Interleukin-1beta/pharmacology , Interleukin-6/pharmacology , Mice , Mice, Nude , MicroRNAs/antagonists & inhibitors , Oligonucleotides, Antisense/metabolism , Sequence Alignment , Transplantation, Heterologous , Tumor Necrosis Factor-alpha/pharmacology , Uterine Cervical Neoplasms/genetics , YY1 Transcription Factor/chemistry , YY1 Transcription Factor/geneticsABSTRACT
Two ruthenium(II) complexes, [Ru(L)2(p-tFMPIP)](ClO4)2 (L = bpy, 1; phen, 2; p-tFMPIP = 2-(4-(trifluoromethyphenyl)-1H-imidazo[4,5f][1,10] phenanthroline)), were prepared by microwave-assisted synthesis technology. The inhibitory activity evaluated by MTT assay shown that 2 can inhibit the growth of MDA-MB-231 cells with inhibitory activity (IC50) of 16.3 µM, which was related to the induction of apoptosis. Besides, 2 exhibit low toxicity against normal HAcat cells. The inhibitory growth activity of both complexes related to the induction of apoptosis was also confirmed. Furthermore, the studies on the interaction of both complexes with c-myc G4 DNA shown that 1 and 2 can stabilize the conformation of c-myc G4 DNA in groove binding mode, which has been rational explained by using DFT theoretical calculation methods. In a word, this type of ruthenium(II) complexes can act as potential apoptosis inducers with low toxicity in clinic by stabilizing c-myc G4 DNA.
