MiR-205-3p suppresses bladder cancer progression via GLO1 mediated P38/ERK activation.

MicroRNAs (miRNAs) have been reported to serve as potential biomarkers in bladder cancer and play important roles in cancer progression. This study aimed to investigate the biological role of miR-205-3p in bladder cancer. We showed that miR-205-3p was significantly down-regulated in bladder cancer tissues and cells. Moreover, overexpression of miR-205-3p inhibited bladder cancer progression in vitro. Then we confirmed that GLO1, a downstream target of miR-205-3p, mediated the effect of miR-205-3p on bladder cancer cells. In addition, we found that miR-205-3p inhibits P38/ERK activation through repressing GLO1. Eventually, we confirmed that miR-205-3p inhibits the occurrence and progress of bladder cancer by targeting GLO1 in vivo by nude mouse tumorigenesis and immunohistochemistry. In a word, miR-205-3p inhibits proliferation and metastasis of bladder cancer cells by activating the GLO1 mediated P38/ERK signaling pathway and that may be a potential therapeutic target for bladder cancer.

A variant rs6214 within IGF-1 confers risk for ulcerative colitis in Chinese Han populations.

Insulin growth factor-1 (IGF-1) has been found to correlate with various diseases such as cancer and cardiovascular diseases including ulcerative colitis (UC). The present study aimed to investigate the plausible association of rs6214 (C > T) within IGF-1 and UC susceptibility in Chinese Han populations. A total of 977 UC patients and 1029 healthy controls were enrolled, and rs6214 was genotyped with PCR and direct sequencing on the ABI 3730XL DNA analyzer platform. Logistic regression analysis was applied for the correlation of rs6214 and UC susceptibility via calculation of odds ratio (OR) with a 95% confidence interval (95% CI) adjusted for age and sex under different genetic models. The difference of clinical parameters between genotypes was measured by one-way analysis of variance (ANOVA). Additional functional assays were conducted to establish the probable relationship. The results indicated that the T allele of rs6214 showed roughly 37% greater risk for UC risk in the additive model (OR = 1.37, 95% CI = 1.21-1.55, P < 0.000001) when compared with C allele carriers, and the pattern was similar in other three genetic models. Further stratified analysis suggested that the association was particularly noteworthy in UC patients with extensive colitis and severe condition. Moreover, the blood level of IGF-1 was downregulated in UC patients, and the mRNA level was lower in T allele carriers in rectal tissues of UC cases. Additional luciferase assay demonstrated that rs6214 regulates IGF-1 expression via promoting miR-2053. Collectively, rs6214 increased UC susceptibility and suppresses IGF-1 expression by enhancing miR-2053 binding. The current findings provided evidence that rs6214 is a promising biomarker for UC prediction and prognosis.

LINC01315 silencing inhibits the aggressive phenotypes of colorectal carcinoma by sponging miR-205-3p.

Long non-coding RNAs (lncRNAs) are important regulatory factors in the progression of cancers. In this study, we investigated the molecular mechanism of long intergenic non-coding 01315 (LINC01315) in inhibiting the aggressive characteristics of colorectal carcinoma (CRC) cells. We proved that LINC01315 was significantly upregulated in CRC. Knockdown of LINC01315 decreased CRC cell growth and invasion in vitro. Bioinformatics analysis and a luciferase reporter experiment showed direct binding between LINC01315 and miR-205-3p. Furthermore, LINC01315 positively modulated protein kinase AMP-activated catalytic subunit α 1 (PRKAA1) expression by serving as a "sponge" for miR-205-3p. Moreover, LINC01315 regulated the growth and invasive phenotypes of CRC cells by sponging miR-205-3p. Downregulation of LINC01315 remarkedly impaired the tumorigenicity of CRC cells in vivo in a transplanted tumour model. Altogether, our results demonstrated that downregulation of LINC01315 suppresses CRC progression by sponging miR-205-3p.

Down-Regulation of miR-2053 Inhibits the Development and Progression of Esophageal Carcinoma by Targeting Fyn-Related Kinase (FRK).

BACKGROUND: MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of cancers including esophageal carcinoma (ESCA). Increasing numbers of miRNAs have been identified to be important regulators in the progression of ESCA by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in ESCA need sufficient elucidation. AIMS: In the present study, the function of miR-2053 was investigated in ESCA cells. METHODS: The expression of miR-2053 was detected in four different ESCA cell lines (Eca109, Ec9706, KYSE30, and TE-1 cells) and normal cell line (HEEC) by qRT-PCR. Cell proliferation, migration, and invasion abilities after knockdown of miR-2053 were assessed by CCK-8 assay, scratch assay, and transwell assay, respectively. Cell cycle of ESCA cells was detected by flow cytometric analysis. Expression of proteins in ESCA cells was detected by Western blot analysis. RESULTS: The results showed that the expression of miR-2053 was remarkably up-regulated in ESCA tissues and cells lines. Down-regulation of miR-2053 markedly inhibited cell proliferation, migration, and invasion and markedly induced cell cycle arrest and cell apoptosis in ESCA cell lines. Fyn-related kinase (FRK) was a target gene of miR-2053. Moreover, down-regulation of miR-2053 mediated the protein kinase B (AKT)/mammalian target of rapamycin and Wnt3a/ß-catenin signaling pathway in ESCA cell lines. CONCLUSIONS: Our results together suggest the potential of regulating miR-2053 expression against development and progression of esophageal carcinoma by targeting FRK.

miR-205-3p promotes proliferation and reduces apoptosis of breast cancer MCF-7 cells and is associated with poor prognosis of breast cancer patients.

BACKGROUND: To study the expression of microribonucleic acid (miR)-205 in breast cancer and its effects on the proliferation and apoptosis of breast cancer cells. METHODS: Breast cancer cell line MCF-7 cells with stable expression of miR-205-3p were constructed. Cell proliferation, invasion, and apoptosis were detected via MTT assay, transwell assay, and flow cytometry, respectively. The expressions of Ezrin, LaminA/C, cleaved caspase-3, Bcl-2, and Bax were detected via Western blotting. The expressions of miR-205-3p in breast cancer tissues and para-carcinoma tissues were detected via quantitative PCR (qPCR). RESULTS: In transfection group, cell proliferation and invasion capacities were increased significantly (P < 0.01), but apoptotic cells were significantly reduced (P < 0.01). In addition, the expressions of Ezrin, LaminA/C, and cleaved caspase-3 in the transfection group were significantly decreased (P < 0.01), but the Bcl-2/Bax ratio was significantly increased (P < 0.01). The miR-205-3p expression in tumor tissues of breast cancer patients was significantly higher than that in para-carcinoma tissue, but Ezrin, LaminA/C, and cleaved caspase-3 expressions in tumor tissues were remarkably declined (P < 0.01), while the Bcl-2/Bax ratio was remarkably increased (P < 0.01). Moreover, the 5-year survival of patients with high expression of miR-205-3p was significantly shorter than patients with normal or low expression (P < 0.01). CONCLUSION: Highly expressed miR-205-3p can promote the proliferation and invasion and reduce the apoptosis of breast cancer cells, and the high expression of miR-205-3p can significantly reduce the survival time of patients.

miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4.

Ovarian cancer is one of the major gynaecological malignancies and a leading cause of cancer-related deaths worldwide. Dysregulation of miR-2053 has been reported in numerous types of cancer; however, its function in ovarian cancer remains largely unknown. In our study, the roles of miR-2053 during the development of ovarian cancer were investigated. miR-2053 expression was examined in ovarian cancer specimens and cells. Furthermore, the detailed functions and downstream targets of miR-2053 were identified. Briefly, the levels of miR-2053 were assessed in ovarian cancer tissues and paired non-cancerous samples, as well as in ovarian cancer cells using reverse transcription-quantitative polymerase chain reaction. The proliferation of cells was determined by cell counting kit-8 kit, and the levels of PCNA were also examined using immunostaining. Cell migration and invasion were evaluated using Transwell assay, and E-cad expression was assessed by immunostaining. In addition, cell apoptosis was determined by flow cytometry, and the expression of cleaved caspase-3 was examined using western blotting. The results revealed the downregulation of miR-2053 in ovarian cancer tissues and cells. Moreover, miR-2053 mimics suppressed the proliferation, migration, and invasion of ovarian cancer cells, while cell apoptosis was promoted. In addition, SOX4 was a putative downstream molecule of miR-2053 in ovarian cancer. Furthermore, SOX4 is involved in miR-2053-regulated growth and metastasis of ovarian cancer cells. In summary, miR-2053 and its novel target SOX4 could serve essential roles during tumour development of ovarian cancer, more importantly, miR-2053/SOX4 axis may be novel candidate for targeted therapy for patients with ovarian cancer.

MicroRNA-2053 involves in the progression of esophageal cancer by targeting KIF3C.

This study aimed to explore the role of micorRNA-2053 in esophageal cancer development. The expression level of miR-2053 in esophageal cancer cell lines was detected. After cell transfection, the effects of miR-2053 overexpression on proliferation, apoptosis, migration and invasion of esophageal cancer cells were determined. Moreover, the potential molecular mechanism was explored by measuring the epithelial-mesenchymal transition (EMT) and apoptosis-related proteins. Luciferase reporter assay was conducted to investigate the target gene of miR-2053. The protein expressions of PI3K/AKT pathway associated factors were detected after overexpression of miR-2053 or administration with the pathway inhibitor LY294002. The miR-2053 was downregulated in esophageal cancer cell lines. Overexpression of miR-2053 inhibited cell proliferation, migration and invasion while promoted apoptosis. Molecular mechanism elucidated that miR-2053 could reduce EMT and elevate the expression of pro-apoptotic proteins. Further study found that overexpressed miR-2053 could negatively regulate KIF3C and involve in PI3K/AKT signaling pathway. Our study demonstrated the downregulation of miR-2053 in esophageal cancer. Downregulation of miR-2053 involved in the proliferation, apoptosis, migration and invasion of esophageal cancer cells through upregulating KIF3C expression and activating the PI3K/AKT signaling pathway. miR-2053 may have the potential in clinical treatment of esophageal cancer.

Upregulation of Linc00284 Promotes Lung Cancer Progression by Regulating the miR-205-3p/c-Met Axis.

Lung cancer (LC) is a malignant tumor with the highest incidence and mortality rates worldwide. Linc00284, a long non-coding RNA, is a newly discovered regulator of LC. This study aimed to explore the role of Linc00284 in LC progression. Gene expression levels were detected by RT-qPCR and/or western blot analysis. Cell migratory and invasive capabilities were measured by wound healing and transwell assays. Subcutaneous xenograft models were constructed to examine tumor growth of LC cells. Data showed that Linc00284 was significantly upregulated in LC tissues compared to adjacent normal lung tissues and predicted poor prognosis in patients with LC. In vitro, Linc00284 was highly expressed in LC cells and was mainly localized in the cytoplasm. Mechanistically, Linc00284 directly bound to miR-205-3p, leading to the upregulation of c-Met expression. A significant negative correlation was observed between Linc00284 and miR-205-3p expression levels, and the Linc00284 level was positively correlated with the c-Met expression. Linc00284/miR-205-3p/c-Met regulatory axis promotes LC cell proliferation, migration, and invasion. Furthermore, the in vivo results indicated that Linc00284 knockdown markedly suppressed tumor growth. Taken together, these data suggest that Linc00284 facilitates LC progression by targeting the miR-205-3p/c-Met axis, which may be a potential target for LC treatment.

miR-205-3p Functions as a Tumor Suppressor in Ovarian Carcinoma.

Ovarian cancer (OC) represents the most lethal form of gynaecologic cancers in developed countries. To develop a better therapeutic against OC, characterizing new classes of molecular regulators such as microRNAs (miRNAs) involved in OC tumorigenesis becomes immensely important. We used human OC cell lines to study the expression pattern of miRNA-205-3p. We then employed miRNA-205-3p mimic and inhibitor to elucidate its functional role in OC cells. Downstream target of miRNA-205-3p was characterized in OC cells with luciferase gene reporter assay and Western blotting. Its functional role in OC was also investigated with the siRNA approach. Lastly, we assessed the expression change of miRNA-205-3p and its newly identified target in human OC tissues. miR-205-3p was downregulated in five human OC lines tested. Over-expressing miR-205-3p reduced OC cell proliferation and migration. MAPK10 was identified as a direct target of miR-205-3p. Knocking down MAPK10 suppressed OC cell growth and migration. In contrast, knocking down miR-205-3p promoted clonogenicity of primary ovary cells. In clinical samples, miR-205-3p and MAPK10 expressed inversely in accordance with their expression patterns in OC cells. miR-205-3p was shown as a novel tumor suppressor in OC via inhibiting the MAPK10 pathway. This new finding may inspire new personalized treatment for OC.

Long noncoding RNA MALAT1 regulates apoptosis in ischemic stroke by sponging miR-205-3p and modulating PTEN expression.

Ischemic stroke has been considered to be one of the major causes of disability worldwide which related to multiple pathological processes including apoptosis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), is one of the long non-coding RNA (lncRNA) know as a regulator for cell apoptosis. However, further and deeper cellular and molecular mechanism in stroke model remains unclear. The results showed MALAT1 was down-regulated in OGD-induced apoptosis and related with miR-205-3p expression. Knockdown of MALAT1 promote OGD-induced apoptosis, decreased the cell viability, inhibit the caspase-3 activation. Moreover, MALAT1 acts as a competing endogenous RNA (ceRNA) for miR-205-3p and further regulate PTEN expression protect OGD-induced apoptosis. Altogether, these results suggest that MALAT1 may suppress the apoptosis in ischemic stroke and function as a ceRNA for miR-205-3p to modulate PTEN expression. These findings may provide a novel therapeutic target for treating ischemic stroke.

Differential miRNA expression profiling reveals miR-205-3p to be a potential radiosensitizer for low- dose ionizing radiation in DLD-1 cells.

Enhanced radiosensitivity at low doses of ionizing radiation (IR) (0.2 to 0.6 Gy) has been reported in several cell lines. This phenomenon, known as low doses hyper-radiosensitivity (LDHRS), appears as an opportunity to decrease toxicity of radiotherapy and to enhance the effects of chemotherapy. However, the effect of low single doses IR on cell death is subtle and the mechanism underlying LDHRS has not been clearly explained, limiting the utility of LDHRS for clinical applications. To understand the mechanisms responsible for cell death induced by low-dose IR, LDHRS was evaluated in DLD-1 human colorectal cancer cells and the expression of 80 microRNAs (miRNAs) was assessed by qPCR array. Our results show that DLD-1 cells display an early DNA damage response and apoptotic cell death when exposed to 0.6 Gy. miRNA expression profiling identified 3 over-expressed (miR-205-3p, miR-1 and miR-133b) and 2 down-regulated miRNAs (miR-122-5p, and miR-134-5p) upon exposure to 0.6 Gy. This miRNA profile differed from the one in cells exposed to high-dose IR (12 Gy), supporting a distinct low-dose radiation-induced cell death mechanism. Expression of a mimetic miR-205-3p, the most overexpressed miRNA in cells exposed to 0.6 Gy, induced apoptotic cell death and, more importantly, increased LDHRS in DLD-1 cells. Thus, we propose miR-205-3p as a potential radiosensitizer to low-dose IR.