Abstract
MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.
Highlights
In the past few years, non-coding RNAs including microRNA and long non-coding RNA have been widely reported as a new class of clinical biomarkers and potential therapeutic targets for cancers.[3,4] As highly conserved small non-coding RNAs with sizes of 20–25 nucleotides, miRNAs could negatively regulate gene expression at post-transcriptional level by directly binding to the 3′-untranslated region (3′-UTR) of target messenger RNA to induce mRNA deregulation or translational repression.[5]
We found that miR-92b, which could act as an oncogene in many cancers but was rarely reported in hepatocellular carcinoma (HCC), was one of the upregulated miRNAs in HCC tissues compared with adjacent non-tumor liver tissue (ANLT) (Figure 1a)
More and more evidences have indicated that the deregulation of miRNAs might be involved in progression of many cancers including HCC.[16] miRNA expression profiling has been used as an approach for identification of molecular biomarkers for tumor occurrence, classification and prognosis.[17,18]
Summary
In the past few years, non-coding RNAs including microRNA (miRNA) and long non-coding RNA (lncRNA) have been widely reported as a new class of clinical biomarkers and potential therapeutic targets for cancers.[3,4] As highly conserved small non-coding RNAs with sizes of 20–25 nucleotides, miRNAs could negatively regulate gene expression at post-transcriptional level by directly binding to the 3′-untranslated region (3′-UTR) of target messenger RNA (mRNA) to induce mRNA deregulation or translational repression.[5]. The lncRNA X-inactive specific transcript (XIST) and miR-152 could interact with and repress each other, acting as crucial regulators for function of human glioblastoma stem cells.[11] limited knowledge is available concerning the relationship between lncRNA and miRNA in the carcinogenesis of HCC, which needs to be well documented. For the first time we reported that miR-92b was upregulated in tumor tissue and plasma of HCC patients, which in turn promoted the proliferation and
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