Down-regulation of miR-497 is associated with poor prognosis in renal cancer

Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor with high mortality. Recent study indicated that microRNAs (miRNAs) played critical roles in tumor progression. The aim of this study was to investigate the expression, biological role and clinical significance of miR-497 in ccRCC. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of miR-497 in renal cancer cell lines and ccRCC tissues. The association between miR-497 expression and overall survival was estimated by the Kaplan-Meier method. Gain of function assays were performed in the 786-O renal cancer cell line. Results: Expression of the miR-497 was significantly decreased in renal cancer cell lines and ccRCC tissues when compared with normal human proximal tubule epithelial cells and adjacent non-tumor tissues. Decreased miR-497 expression was significantly associated with tumor stage, histological grade and lymph node metastases. Significantly shorter overall survival was observed in patients with lower expression of the miR-497. Overexpression of miR-497 significantly inhibited renal cancer cell proliferation, migration and invasion. Conclusions: Our results demonstrated that miR-497 was decreased in ccRCC tissues and may provide a potential prognostic biomarker and a potential target for therapeutic intervention.     

MicroRNA-139-5p inhibits cell proliferation and invasion by targeting insulin-like growth factor 1 receptor in human non-small cell lung cancer

Introduction: Increasing evidence suggested that microRNAs (miRNAs) play a critical role in tumorigenesis. Decreased expression of miRNA-139-5p has been observed in various types of cancers. However, the biological function of miRNA-139-5p in non-small cell lung cancer (NSCLC) is still largely unknown. Methods: Quantitative real-time PCR (qRT-PCR) was used to explore the expression level of miRNA-139-5p in NSCLC tissues and cell lines. Then, we investigated the role of miRNA-139-5p to determine its potential roles on lung cancer cell proliferation, migration and invasion in vitro. A luciferase reporter assay was performed to confirm the target gene of miRNA-139-5p and the results were validated in renal cancer cells. Results: miRNA-139-5p was significantly decreased in NSCLC tissues and cell lines. Over-expression of miRNA-139-5p could inhibit lung cancer cell proliferation, migration, and invasion in vitro. Furthermore, we identified insulin-like growth factor 1 receptor (IGF1R) as a target of miR-139-5p and miR-139-5p function as a tumor suppressor via targeting IGF1R in NSCLC. Conclusions: Our results indicated that miR-139-5p acts as a tumor suppressor in NSCLC partially via down-regulating IGF1R expression.     

Low expression of miR-99b promotes progression of clear cell renal cell carcinoma by up-regulating IGF1R/Akt/mTOR signaling

Objective: Dysfunctions of microRNAs have been implicated in the progression of clear cell renal cell carcinoma (ccRCC). Here, we investigated the roles of miR-99b and miR-99b* in ccRCC development. Methods: The expression levels of miR-99b and miR-99b* in tumor and tumor-adjacent tissues from ccRCC patients were quantified by quantitative Real-Time PCR (qRT-PCR). MicroRNA mimics and inhibitors were employed to evaluate the functions of miR-99b and miR-99b*. The effects of miR-99b on the proliferation and migration of ccRCC cells were analyzed by MTT and wound-healing assays, respectively. The effect of miR-99b on the expression of its target gene IGF1R and mTOR was determined by western blotting and qRT-PCR. Results: The abundances of miR-99b and miR-99b* were lower in ccRCC tissues than in the tumor-adjacent tissues from patients. Similarly, the expression of these two microRNAs was higher in the normal kidney HK-2 cells than in the ccRCC cell lines. Moreover, miR-99b and miR-99b* inhibited the proliferation and migration of ccRCC cells. MiR-99b was found to down-regulate IGF1R and mTOR expression, likely through targeting their mRNAs to induce degradation. Consistently, the mRNA levels of IGF1R and mTOR were higher in ccRCC tissues than in the tumor-adjacent tissues, and Akt, a downstream factor of IGF1R, was highly activated correspondingly in ccRCC tissues. Conclusion: The low expression of miR-99b and miR-99b* contributes to ccRCC development and miR-99b acts as an onco-suppressor by suppressing IGF1R and mTOR expression to down-regulate IGF1R/AKT/mTOR signaling.     

miR-145 suppressed human retinoblastoma cell proliferation and invasion by targeting ADAM19

MicroRNAs (miRNAs) play critical roles in retinoblastoma (RB) initiation and progression, aberrant expression of miR-145 had been frequently reported in cancer studies. However, the role and mechanism of its function in RB is still unclear. In this study, our data showed that miR-145 was downregulated in RB tissues and cell lines. Overexpression of miR-145 suppressed RB cell proliferation, migration and invasion in vitro. ADAM19 was identified as a direct target of miR-145. Silencing of ADAM19 significantly inhibited RB cell proliferation, migration and invasion. In addition, a reverse correlation between miR-145 and ADAM19 expression was noted in RB tissues. Taken together, these findings suggested that miR-145 functions as a tumor suppressor in RB by directly targeting ADAM19. miR-145 could be an anticancer therapeutic target for RB patients.     

High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma

Introduction: Long non-coding RNAs (lncRNAs) play a key role in cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNAs SPRY4-IT1 has recently been identified to be involved in tumorigenesis of several cancers such as non-small cell lung cancer and esophageal squamous cell carcinoma. However, the role of SPRY4-IT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: The expression of SPRY4-IT1 was examined in ccRCC patients and renal cancer cell lines by using quantitative real-time PCR (qRT-PCR). The relationship between SPRY4-IT1 level and clinicopathological parameters of ccRCC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in renal cancer cell line 786-O. In vitro assays were performed to further explore its role in renal cancer progressio. Results: The relative level of SPRY4-IT1 was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. And higher expression of SPRY4-IT1 was found in renal cancer cell lines compared with the normal human proximal tubule epithelial cell line HK-2. The ccRCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. Multivariate analyses by Cox’s proportional hazard model revealed that expression of SPRY4-IT1 was an independent prognostic factor in ccRCC. In vitro assays, our results indicated that knockdown of SPRY4-IT1 reduced renal cancer cell proliferation, migration, and invasion. Conclusions: Our data suggested that lncRNA SPRY4-IT1 might be considered as a potential prognostic indicator and a potential target for therapeutic intervention in RC.     

miR-185 acts as a tumor suppressor by targeting AKT1 in non-small cell lung cancer cells

Increasing evidence has shown that microRNAs play critical roles in the initiation and progression of non-small cell lung cancer (NSCLC). miR-185 is deregulated in various cancers, whereas its functional mechanism in NSCLC is still unclear. Here, we confirmed that the expression of miR-185 was significantly down-regulated in NSCLC tissues and cell lines. miR-185 over-expression caused significant suppression of in vitro cell proliferation, migration and invasion, and in vivo tumor growth. We subsequently identified that AKT1 was a target gene of miR-185. Re-expression of AKT1 could partially rescue the inhibitory effects of miR-185 on the capacity of NSCLC cell proliferation and motility. Collectively, we conclude that miR-185 has a critical function by blocking AKT1 in NSCLC cells, and it may be a novel therapeutic agent for miRNA based NSCLC therapy.     

Blocking lncRNA MIR155HG/miR-155-5p/-3p inhibits proliferation,invasion and migration of clear cell renal cell carcinoma

This study aimed to investigate the effect of blocking the MIR155HG/miR-155-5p/-3p axis on proliferation, invasion and migration of clear cell renal cell carcinoma. RT-qPCR was used to detect the expression of MIR155HG, miR-155-5p, miR-155-3p in clear cell renal cell carcinoma cell lines. To study the effects of blocking LncRNA MIR155HG and interfering with miR-155-5p and miR-155-3p on the biological function. The g proliferation of tumor was detected by CCK-8, and the cell invasion and migration abilities were detected by wound healing and transwell experiments. Western blot analyzed protein levels of KI67, PCNA, MMP2 and MMP9. Furthermore, TargetScan and miRDB were used to predict the co-target gene of miR-155-3p and miR-155-5p, and the functional analysis of co-target genes was performed using the DAVID. In the current research, the expression of MIR155HG was increased in ccRCC. Interference of MIR155HG inhibited the cellular functions of ccRCC cells, which was reversed by overexpression of miR-155-3p and miR-155-5p.In addition, MIR155HG interference repressed the expression of miR-155-5p and miR-155-3p in ccRCCs, while inhibition of miR-155-5p and miR-155-3p restrained the proliferation, invasion and migration of ccRCCs. Bioinformatics software analysis showed 13 co-targeting genes of miR-155-3p and miR-155-5p. Functional analysis presented that the target genes of miR-31-3p were involved in numerous of biochemical processes and pathways.Blocking lncRNA MIR155HG/miR-155-5p/-3p inhibits proliferation, invasion and migration of renal clear cell carcinoma, which provided a new method for early diagnosis and precise treatment of ccRCC.     

miR-338-3p inhibits the proliferation and migration of gastric cancer cells by targeting ADAM17

Background: MicroRNAs (miRNA) have been documented playing a critical role in cancer progression. Although miR-338-3p has been implicated in several cancers, its role in gastric cancer is still unknown. The aim of our study was to investigate the role of miR-338-3p in gastric cancer progression. Methods: Expression levels of miR-338-3p in gastric cancer cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR). The effect of miR-338-3p on proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays. Furthermore, luciferase reporter assay was conducted to confirm the target gene of miR-338-3p, and the results were validated in gastric cancer cells. Results: In the present study, we found that miR-338-3p was down-regulated in both gastric cancer cell lines and tissues. Enforced expression of miR-338-3p inhibited proliferation, migration and invasion of gastric cancer cells in vitro. Moreover, we identified A disintegrin and metalloproteinase 17 (ADAM17) gene as potential target of miR-338-3p. Importantly, ADAM17 rescued the miR-338-3p mediated inhibition of cell proliferation, migration and invasion. Conclusions: Our study suggested that miR-338-3p is significantly decreased in gastric cancer, and inhibits cell proliferation, migration and invasion partially via the downregulation of ADAM17. Thus, miR-338-3p may represent a potential therapeutic target for gastric cancer intervention.     

MicroRNA-130a inhibits cell proliferation,invasion and migration in human breast cancer by targeting the RAB5A

MiR-130a has been demonstrated to play important roles in many types of cancers. Nevertheless, its biological function in breast cancer remains largely unknown. In this study, we found that the expression level of miR-130a was down-regulated in breast cancer tissues and cells. Overexpression of miR-130a was able to inhibit cell proliferation, invasion and migration in MCF7 and MDA-MB-435 cells. With the bioinformatics analysis, we further identified that RAB5A was a directly target of miR-130a, and its mRNA and protein level was negatively regulated by miR-130a. Immunohistochemistry verified RAB5A was upregulated in breast cancer tissues. Therefore, the data reported here demonstrate that miR-130a is an important tumor suppressor in breast cancer, and imply that miR-130a/RAB5A axis have potential as therapeutic targets for breast cancer.     

MicroRNA-137 inhibits cell migration and invasion by targeting bone morphogenetic protein-7 (BMP7) in non-small cell lung cancer cells

MicroRNA-137 (miR-137) was reported to be dysregulated in several human cancers. However, the function and mechanism of miR-137 in non-small cell lung cancer (NSCLC) is still unclear. In the current study, we explored the role of miR-137 in NSCLC progression. Using qRT-PCR, our data showed that miR-137 was significantly down-regulated in NSCLC tissues and cell lines. In vitro functional assay, we found that over-expression of miR-137 suppressed NSCLC cells proliferation, migration and invasion, indicating that miR-137 could act as a tumor suppressor in NSCLC progression. In addition, bone morphogenetic protein-7 (BMP7) was identified as a target of miR-137 in NSCLC cells, Luciferase reporter assay suggested that miR-137 directly targeted 3’-UTR of BMP7, and correlation analysis revealed that BMP7 inversely correlated with miR-137 in NSCLC tissues. Furthermore, Restoration of BMP7 remarkably reversed the tumor suppressive effects of miR-137 on NSCLC cell proliferation, migration, and invasion. Taken together, our findings suggested that miR-137/BMP7 axis could contribute to the progression of NSCLC, suggesting miR-137 as a potential therapeutic target for the treatment of NSCLC.     

miR-34c-3p inhibits cell proliferation,migration and invasion of hepatocellular carcinoma by targeting MARCKS

Recent studies have shown that microRNA-34c-3p (miR-34c-3p) is down-regulated in various types of cancers and involved in tumor growth, invasion and metastasis. However, the roles of miR-34c-3p in hepatocellular carcinoma (HCC) are poorly understood. In this study, the expression profile of miR-34c-3pin HCC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of miR-34c-3p expression and clinicopathological characteristics were analyzed. The biological role of MiR-34c-3pin cell proliferation, migration and invasion was examined. In addition, the targets of miR-34c-3p were identified. The results showed that miR-34c-3p expression was significantly down-regulated in HCC tissues and cell lines; low expression level of miR-34c-3p was correlated with vascular invasion and advanced TNM stage. In vitro functional assays showed that overexpression of miR-34c-3pin HepG2 and Huh7 cells significantly reduced cell proliferation, migration and invasion. Furthermore, target analysis and luciferase assay identified myristoylated alanine-rich protein kinase c substrate (MARCKS) as a specific target of miR-34c-3p. Knockdown of MARCKS in HepG2 cells reduced cell migration and invasion, but not cell proliferation. Taken together, our findings implicate the potential application of miR-34c-3p as a tumor suppressor in cancer therapy.     

MiR-1228 promotes breast cancer cell growth and metastasis through targeting SCAI protein

Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that miR-1228 was up-regulated in breast cancer cell lines and tissues. Ectopic expression of miR-1228 mimics leads to promoted cell growth, invasion and migration. Using bioinfomatic analysis and 3’UTR luciferase reporter assay, we determined SCAI can be directly targeted by miR-1228, which can down-regulate endogenous SCAI protein level. Furthermore, our findings demonstrate that SCAI was down-regulated in breast cancer cell lines and tissues. Rescue experiment demonstrated that miR-1228 promoted cell growth is attenuated by over-expression of MOAP1 and miR-1228 promoted cell invasion and migration can be attenuated by over-expression of SCAI. Taken together, this study provides evidences that miR-1228 serves as an oncogene to promote breast cancer proliferation, invasion and migration, which may become a critical therapeutic target for breast cancer treatment.     

MicroRNA-145 suppresses cell migration and invasion by targeting paxillin in human colorectal cancer cells

A number of cancers show increased expression of paxillin which plays a central role in tumor progression, including colorectal cancer. However, the mechanisms causing paxillin upregulation remains unclear. In our study, bioinformatics analyses suggested that paxillin is predicted to be a direct target of miR-145. We firstly identified paxillin as a new target of miR-145 and demonstrated that miR-145 inhibits paxillin expression by binding to the paxillin mRNA 3’UTR. Therefore, we assume overexpression of paxillin induced by suppression of miR-145 may promote cell migration and invasion. We detected the expression of paxillin and miR-145 in human colorectal cancer tissues by real-time quantitative PCR. Higher expression of paxillin and lower expression of miR-145 was observed in colorectal cancer tissues than corresponding paracancerous tissue. Moreover, the expression of paxillin was negatively correlated with miR-145 expression. A dual-luciferase reporter assay was used to confirm that paxillin was a direct target of miR-145. In CRC cell lines, overexpression of miR-145 could downregulate paxillin protein expression levels, and ectopic overexpression of miR-145 mimics or inhibitor could inhibit or promote cell migration, invasion, proliferation and clone formation in vitro. Taken together, these data suggested that miR-145 plays a pivotal role in colon cancer through inhibiting cell proliferation migration and invasion, and miR-145 may serve as a tumor suppressor by targeting paxillin gene.     

miR-106a promotes growth and metastasis of non-small cell lung cancer by targeting PTEN

MicroRNAs are a class of small non-coding RNAs that play essential roles in cancer development and progression. Recent studies suggested that abnormal expression of miRNAs occurs frequently in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues. In this study, we investigated the expression and the biological roles of miR-106a in non-small cell lung cancer. Our results showed that miR-106a was up-regulated in NSCLC tissues and cell lines. Inhibition of miR-106a in NSCLC cells substantially inhibited cell proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-106a, and over-expression of miR-106a suppressed PTEN by direct binding to its 3’-untranslated region (3’-UTR). Furthermore, the presence of miR-106a was inversely correlated with PTEN in NSCLC tissues. Overall, this study suggested that miR-106a inhibited the growth and metastasis of NSCLC cells by decreasing PTEN expression. These data provide novel insights with potential therapeutic applications for the treatment of NSCLC.     

miR-183在人乳腺癌中表达及意义

目的:研究miR-183在人乳腺癌组织和细胞株中表达状况及其对乳腺癌细胞生物学行为的影响。方法:使用实时定量PCR方法检测miR-183在人乳腺细胞株和临床乳腺病变组织中表达;使用脂质体介导的miRNA转染技术,检测转染miR-183后对乳腺癌细胞增殖、侵袭和迁移活力的影响。结果:高度侵袭力的乳腺癌细胞株miR-183表达较低侵袭乳腺细胞株显著下调(P<0.01);临床人乳腺癌组织中miR-183表达较乳腺良性病变组织显著下调(P<0.01);使用miR-183抑制物和模拟物分别转染乳腺癌细胞株MCF-7和MDA-MB-231后,乳腺癌细胞侵袭和迁移活力分别上调和下调(P<0.05),而细胞增殖活力改变不明显(P>0.05)。结论:乳腺癌中miR-183表达出现失调。miR-183可能参与了乳腺癌细胞侵袭和迁移过程。     

MiR-449a suppresses cell migration and invasion by targeting PLAGL2 in breast cancer

Background

Breast cancer is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying breast cancer metastasis are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer metastasis. In this study, we aimed to analyze the expression and function of miR-449a in breast cancer.