The morbidity incidence of CC has ranked no. 3 among all malignant tumor diseases in China. CC affects approximately 390,000 new patients in China annually, and the mortality has ranked no. 5 among all malignant tumors. Tumor metastasis is the major cause of death in CC patients. miRNAs are small non-coding RNAs, they induce their degradation or block the translation of the encoded protein via binding to specific complementary sequences in the 3’UTR of target mRNAs. With the diverse abilities, reducing of their expression has might been involved with promoting or suppressing tumor metastasis, providing a new perspective on the metastatic process. As is well-known, miRNAs could promote or inhibit various traits related to tumor aggressiveness such as proliferation, cell migration and invasion in various cancer cell lines. As one member of them, miRNA-135a can produce an identical and active sequence through being encoded by two genes localized on different chromosomes. Current reports have shown that the effects of miRNA-135a on cancer progression are contradictory. Previous researches showed that the expression of miRNA-135a decreased in human gastric cancer, the proliferation of gastric cancer cells was repressed while the apoptosis was promoted [10]. On the other hand, miRNA-135a showed a inhibitive role during the migration and invasion of lung cancer cells, due to targeting a transcription factor [19]. However, the functions and mechanisms of miRNA-135a during tumors are largely unknown[20-23]. Recent studies have demonstrated that miRNA-135a is up-regulated in CC cell lines SW480 and SW620, while in our study, the expression levels of miRNA-135a were significantly increased in CC tissues, which was in accordance with previous studies. With the analysis of clinicopathologic characteristics, the expression levels of miRNA-135a were obviously different between different tumor stage groups, and it was different in lymph node involvement group. They were positively related. The data also showed no correlation between miRNA-135a and many aspects in CC tissues, including age, tumor size, location, differentiation and etc. These results supported the hypothesis that miRNA-135a was involved in CC progression, which might function as an oncogenic factor.
Bach1, a member of the basic leucine zipper transcription factor family, is a critical participant in the process of oxidative stress[24]. Recent researches demonstrate that Bach1 is a widely expressed transcriptional repressor, it takes part in many vital cell processes through the targeted genes, such as cell cycle progression, apoptosis, and the hypoxia response negatively [25-28]. Heme-oxygenase-1 (HO-1),one of the target genes, might be significant in induction of the tumorigenic pathway. The significant increasing expression of HO-1 in various types of cancer is contributed to promote tumor growth and metastasis. Furthermore, Bach1 is recognized to inhibit growth and survival of acute myeloid leukemia (AML) cells by down-regulation of HO-1 expression. Bach1 functions as a repressor of HO-1 in human renal cancer cells, though the possible mechanism has not been established[17,29]. In additional, the up-regulation of HO-1 might inhibit apoptosis of renal cancer cells via activation of the nuclear factor (erythroid-derived 2)-like 2(Nrf2) pathway.[29,30]. Our results show that the expression of Bach1 significantly decreased in CC tissues. With further analysis, there was no difference in tumor I-II stages while the majority decrease was in tumor III-IV stages, which was similar to miRNA-135a. These findings indicated that Bach1 might play a inhibition role during the development of CC, especially in the advanced stages. Additionally, Bach1 and miRNA-135a were negatively correlated. Thus, it could be concluded that miRNA-135a played an oncogenic role in CC through down-regulation of Bach1 at least partially. Bach1 might be one of targets of miRNA-135a. However, our study indicated the potential role of miRNA-135a and Bach1, further research should be needed to explore the exact signal pathway between them during the development of CC.