microRNA-802 accelerates hepatocellular carcinoma growth by targeting RUNX3.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Prognosis is often unfavorable. In this study, the effects of microRNA-802 (miR-802) on HCC progression were assessed in vivo and in vitro. miR-802 was found to be significantly upregulated in HCC tumor tissue compared to paired adjacent nontumor tissue. In vitro, transfection with a miR-802 mimic accelerated SMMC-7721 cellular proliferation, increased accumulation of the cell-cycle S-phase cell populations, as well as cell migration. In vivo injection of a miR-802 agomir promoted HCC proliferation in nude mice. Targets of miR-802 were predicted by miRWalk, miRanda, RNA22, and Targetscan. By luciferase reporter assay RUNX3 was identified as a direct target of miR-802. As judged by western blot analysis, RUNX3 was upregulated when miR-802 was inhibited. These data demonstrate increased miR-802 expression in patients with HCC and that miR-802 overexpression promotes tumor cell growth, in a RUNX3-dependent manner.

miR-802 inhibits the proliferation, invasion, and epithelial-mesenchymal transition of glioblastoma multiforme cells by directly targeting SIX4.

It is well known that the sine oculis homeobox 4 (SIX4) expression is very relevant to the progression of multiple cancers. Moreover, we found that miR-802 could directly target the SIX4. However, the precise mechanism of miR-802 in glioblastoma multiforme (GBM) is still unknown. The aim of this study is to investigate the roles of miR-802/SIX4 axis in GBM. Here, our results showed that the SIX4 expression was obviously increased in GBM tissues and cell lines, and the miR-802 level was distinctly decreased. What is more, the SIX4 expression was negatively related to the miR-802 level in GBM tissues. Furthermore, increased miR-802 level evidently restrained the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of GBM cells. Next, we confirmed that miR-802 could directly target SIX4 by using luciferase reporter assay. Besides, the knockdown of SIX4 had the similar effects with miR-802 overexpression on GBM cells. The inhibitory effects of miR-802 mimic were partially blocked by SIX4 overexpression. Altogether, the overexpression of miR-802 restrained cell proliferation, invasion, and EMT of GBM cells via the regulation of SIX4. SIGNIFICANCE OF THE STUDY: An elevated expression of SIX4 has been observed in colorectal cancer and nonsmall cell lung cancer. However, the precise roles of SIX4 in GBM have not been elucidated. Our study for the first time demonstrated that SIX4 level was significantly upregulated in GBM. Additionally, the knockdown of SIX4 inhibited cell growth, invasion, and the EMT of GBM. Moreover, our data suggested a significant negative correlation between miR-802 and SIX4 expression in GBM. MiR-802 suppressed GBM cell proliferation, invasion, and EMT by directly targeting SIX4, which suggested important roles for miR-802/SIX4 axis in the GBM pathogenesis and its potential application in cancer therapy.

microRNA-802 inhibits cell proliferation and induces apoptosis in human cervical cancer by targeting serine/arginine-rich splicing factor 9.

microRNAs (miRNAs) play crucial roles in cancer development and progression by targeting mRNAs for degradation and/or translational repression. microRNA-802 (miR-802) has been reported as a tumor suppressor and its deregulation is observed in various human cancers. However, the prognostic value of miR-802 and its underlying mechanisms involved in human cervical cancer are poorly investigated. The purposes of this study were to explore the role of miR-802 in cervical cancer and to clarify the regulation of serine/arginine-rich splicing factor 9 (SRSF9) by miR-802. Here, we found that miR-802 was downregulated in both cervical cancer tissues and cell lines. Transfection of a miR-802 mimic into cervical cancer cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and cell apoptosis. In addition, we found that miR-802 could directly target the 3'-untranslated region of SRSF9 and suppress SRSF9 expression. Rescue experiments revealed that overexpression of SRSF9 partially reversed the inhibition effect of miR-802 in cervical cancer cells. Overall, these findings demonstrate that miR-802 functions as a tumor suppressor in cervical cancer by targeting SRSF9, suggesting that miR-802 might serve as a potential therapeutic target in cervical cancer.

Long Non-coding RNA SNHG16 Facilitates Esophageal Cancer Cell Proliferation and Self-renewal through the microRNA-802/PTCH1 Axis.

OBJECTIVE: This research sought to explore the effect and mechanism of long non-coding RNA SNHG16 on esophageal cancer (EC) cell proliferation and self-renewal. METHODS: SNHG16 expression was measured in EC9706 and KYSE150 cells. EC9706 and KYSE150 cells were transfected with Lenti-SNHG16, sh-SNHG16, Lenti-protein patched homolog 1 (PTCH1), miR-802 mimic, or miR-802 inhibitor. Flow cytometry was used to sort cancer stem cells (CSCs) in EC9706 and KYSE150 cells. Cell proliferation in EC cells was measured, in addition to colony and tumorsphere numbers. The possible interactions among SNHG16, PTCH1, and miR-802 were identified by dual luciferase reporter and RNA pull-down assays. The expression of the genes in the Hedgehog pathway was detected. Nude mice were injected with SNHG16-silenced EC9706 cells to observe the tumorigenicity of EC9706 cells. RESULTS: Upregulated SNHG16 expression was found in CSCs, whose expression was decreased during the differentiation of CSCs. SNHG16 or PTCH1 overexpression or miR-802 inhibition promoted the proliferation, colony formation, and tumorsphere formation of EC9706 and KYSE150 cells as well as SOX2, OCT4, Bmi-1, and PTCH1 expression. Consistently, SNHG16 knockdown or miR-802 overexpression inhibited EC progression. Moreover, SNHG16 and PTCH1 were competitively bound to miR-802, and SNHG16 orchestrated the miR-802/PTCH1 axis to activate the Hedgehog pathway. SNHG16 silencing repressed the tumorigenicity of EC9706 in nude mice. CONCLUSION: Conclusively, SNHG16 acts as a sponge of miR-802 to upregulate PTCH1 and activate the Hedgehog pathway, thus promoting EC cell proliferation and selfrenewal.

miR­802 inhibits the epithelial­mesenchymal transition, migration and invasion of cervical cancer by regulating BTF3.

MicroRNA (miR)-802 has been discovered to be involved in the occurrence and development of numerous types of tumor; however, studies into the role of miR­802 in cervical cancer are limited. Therefore, the present study aimed to investigate the regulatory effects of miR­802 in cervical cancer cells. miR­802 expression levels in cervical cancer tissue and cells were analyzed using reverse transcription­quantitative (RT­q)PCR, a dual­reporter luciferase activity assay was used to identify the direct target gene of miR­802, and RT­qPCR and western blotting were performed to determine the relationship between miR­802 and basic transcription factor 3 (BTF3). Cell viability, and migration and invasion were analyzed using Cell Counting Kit­8 and Transwell assays, respectively. Finally, the expression levels of metastasis­associated proteins, N­cadherin and E­cadherin, were determined using RT­qPCR and western blotting. Decreased expression levels of miR­802 were found in cervical cancer tissues and cells, and the overexpression of miR­802 inhibited cell viability, migration and invasion. Moreover, miR­802 was discovered to directly target BTF3 to inhibit its expression. Notably, the overexpression miR­802 markedly reversed the promotive effect of BTF3 on cell viability, in addition to the migratory and invasive abilities of the cells. Simultaneously, the overexpression of miR­802 significantly suppressed epithelial­mesenchymal transition, and the expression levels of matrix metallopeptidase (MMP)2 and MMP9 in cells through regulating BTF3. In conclusion, the present study revealed that miR­802 may suppress cervical cancer progression by decreasing BTF3 expression levels, indicating that it may represent a potential therapeutic target for the treatment and prognosis of patients with cervical cancer.

MicroRNA-802 regulates hepatic insulin sensitivity and glucose metabolism.

The expression level of microRNA-802 (miR-802) is increased in livers of high-fat diet (HFD)-fed mice and obese human subjects; however, the function of miR-802 in the development of obesity-associated insulin resistance remains incompletely understood. Here we studied the potential role of miR-802 in regulating hepatic glucose metabolism and insulin sensitivity. Mice were fed either a standard chow diet or HFD for 12 weeks, and then the HFD mice were infected by injection with an adeno-associated virus expressing miR-802 or miR-802-SP. Six weeks after the injection, we measured blood glucose, plasma insulin, and insulin sensitivity in the mice. In addition, hepatic glucose levels and PI3K-Akt pathway gene expression were analyzed. Adeno-associated viral-mediated overexpression of miR-802 in the livers of HFD mice caused impaired glucose homeostasis and insulin sensitivity, thus giving rise to decreased protein level of pAkts473 and pPI3K, and increased protein levels of pPTEN, G6PC, and GluT2. In contrast, loss of miR-802 function in the liver of HFD mice led to increased pAkts473 and pPI3K, and decreased levels of pPTEN, G6PC, and GluT2, thereby improving glucose metabolism and insulin resistance. Our findings confirmed MiR-802 as a regulator of liver glucose metabolism and insulin signaling.

microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer.

miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial-mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected using MTT assay, and cell apoptosis was evaluated using flow cytometry. Transwell assay was conducted to investigate cell migration and invasion. Expression analysis of a set of EMT markers was performed to explore whether miR-802 is involved in EMT program. Xenograft model was established to investigate the function of miR-802 in carcinogenesis in vivo The direct regulation of Flotillin-2 (Flot2) by miR-802 was identified using luciferase reporter assay. miR-802 was remarkably down-regulated in PCa tissues and cell lines. Gain-of-function trails showed that miR-802 serves as an 'oncosuppressor' in PCa through inhibiting cell proliferation and promoting cell apoptosis in vitro Overexpression of miR-802 significantly suppressed in vivo PCa tumor growth. Luciferase reporter analysis identified Flot2 as a direct target of miR-802 in PCa cells. Overexpressed miR-802 significantly suppressed EMT, migration and invasion in PCa cells by regulating Flot2. We identified miR-802 as a novel tumor suppressor in PCa progression and elucidated a novel mechanism of the miR-802/Flot2 axis in the regulation of EMT, which may be a potential therapeutic target.