MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism

Wang, Bo; Shen, Zhanlong; Jiang, Kewei; Zhao, Gang; Wang, Chunyou; Yan, Yichao; Yang, Yang; Zhang, Jizhun; Shen, Chao; Gao, Zhidong; Ye, Yingjiang; Wang, Shan

doi:10.1186/s12885-015-1438-z

Cited by 78 publications

(64 citation statements)

References 42 publications

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“…Thus, it is urgent to identify the factors involved in metastasis and understand the molecular mechanisms underlying metastatic CRC. At present, it is becoming largely accepted that miRNAs play important roles in cancer invasion and metastasis [24, 25]. Therefore, the identification of metastasis-related miRNAs and clarification of their functional mechanism may reveal the existence of novel predictors or therapeutic targets for the effective prevention or treatment of metastatic CRC patients.…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling

et al. 2016

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The progression of distant metastasis cascade is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumorigenesis and tumor progression in colorectal cancer (CRC). In the present study, by comparing the miRNA expression profiles of CRC tissues and corresponding hepatic metastasis tissues, we established the downregulation of miR-199b in CRC metastasis tissues. The decrease in miR-199b expression was significantly correlated to late TNM stage and distant metastasis. Moreover, Kaplan–Meier curves showed that CRC patients with high expression level of miR-199b had a longer median survival. Functional assays results indicated that the restoration of miR-199b considerably reduced cell invasion and migration in vitro and in vivo, and increased the sensitivity to 5-FU and oxaliplatin. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-199b in CRC. The expression of miR-199b was inversely correlated with SIRT1 in CRC specimens. SIRT1 knockdown produced effects on biological behavior that were similar to those of miR-199b overexpression. Furthermore, through Human Tumor Metastasis PCR Array we discovered KISS1 was one of the downstream targets of SIRT1. Silencing of SIRT1 upregulated KISS1 expression by enhancing the acetylation of the transcription factor CREB. The latter was further activated via binding to the promoter of KISS1 to induce transcription. Thus, we concluded that miR-199b regulates SIRT1/CREB/KISS1 signaling pathway and might serve as a prognosis marker or a novel therapeutic target for patients with CRC.

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Section: Discussionmentioning

confidence: 99%

“…Total RNA extraction and quantitative real-time PCR (qPCR) were conducted according to the manufacture's instruction (Takara, Shiga, Japan), and data analysis was performed as we previously described [25]. The expression level of mRNAs or miRNAs was normalized with reference to GAPDH or U6 RNA, respectively.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling

et al. 2016

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“…Although advancements in treatment have been made, the identification of new prognostic biomarkers and improving the understanding of the molecular mechanisms underlying CRC remains a challenge (3). Therefore, investigating the mechanisms underlying the occurrence and development of CRC, and identifying novel diagnostic biomarkers and effective therapeutics is of high importance (4,5).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA GAS5 inhibits cell proliferation, induces G0/G1 arrest and apoptosis, and functions as a prognostic marker in colorectal cancer

et al. 2017

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Abstract. Colorectal cancer (CRC) is the third most common cancer worldwide and its treatment remains a challenge. Effective control of cell survival and proliferation is critical in the prevention of oncogenesis and successful treatment of cancer. Long non-coding RNAs (lncRNAs) have emerged as primary regulators of carcinogenesis. Growth arrest specific 5 (GAS5), a lncRNA, is known to be aberrantly expressed in several types of cancer, however, the role of GAS5 in CRC remains unclear. In the present study, GAS5 mRNA expression was measured in CRC and adjacent normal mucosa tissue samples from 53 patients using reverse transcription-quantitative polymerase chain reaction analysis, in addition to seven CRC cell lines. GAS5 mRNA expression was observed to be markedly downregulated in human CRC tissues and cell lines. Decreased GAS5 expression was associated with an increase in tumor diameter [odds ratio (OR), 0.176 (95% CI, 0.053-0.586); P=0.003] and later tumor-node-metastasis stage [OR, 0.261 (95% CI, 0.083-0.819); P=0.019]. Patients with decreased GAS5 expression exhibited decreased overall survival rates compared with patients with increased GAS5 expression (P=0.015). The Cox proportional hazards model demonstrated that downregulated GAS5 expression was an independent prognostic factor for CRC (hazard ratio, 0.236; 95% confidence interval, 0.067-0.827; P= 0.024). Functional assays demonstrated that overexpression of GAS5 inhibited cell proliferation and survival, and induced G0/G1 cell cycle arrest and apoptosis; however, knockdown of GAS5 expression enhanced cell proliferation, and reduced G0/G1 arrest and apoptosis. In conclusion, the results of the present study suggest that GAS5 is essential in the control of apoptosis and cell growth in CRC. Therefore, GAS5 may represent a novel prognostic and diagnostic marker of CRC, in addition to being a potential therapeutic target.

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“…miR-217 was also found to be downregulated in colorectal cancer tissues compared with corresponding noncancerous tissues. The low expression level of miR-217 was notably correlated with tumor differentiation and shorter overall survival for patients with colorectal cancer (24). Additionally, miR-217 was found to be downregulated in lung (25), hepatocellular (26) and clear cell renal cell carcinoma (27) and pancreatic ductal adenocarcinoma (28).…”

Section: Discussionmentioning

confidence: 97%

“…miR-217 has been verified as a tumor suppressor in osteosarcoma via blockade of the WAS protein family member 3 and Wnt5a (21,22,30). In colorectal cancer, enforced miR-217 expression targeted astrocyte-elevated gene-1 to decrease cell growth, colony formation, migration and invasion by promoting apoptosis and G 0 /G 1 phase arrest (24). In hepatocellular carcinoma, endogenous miR-217 expression inhibited cell invasion by directly targeting E2F transcription factor 3 (26).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

Xiao

Deng

et al. 2017

Oncology Letters

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Abstract. Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)-217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR-217 in AML have not yet been recognized. The expression of miR-217 was determined by quantitative polymerase chain reaction (qPCR). Following transfection with miR-217 mimics, an MTT assay, chemosensitivity assay, cell apoptosis assay and western blot analysis were performed in AML cell lines. Functional assays were also performed to explore the effects of endogenous Kirsten rat sarcoma viral oncogene homolog (KRAS) in AML. The results revealed that miR-217 was downregulated in patients with AML. Overexpression of miR-217 inhibited cellular proliferation and enhanced cell chemosensitivity to doxorubicin by the cell apoptosis pathway in AML cells. A dual-luciferase reporter assay demonstrated that KRAS was a direct target gene of miR-217 in vitro. qPCR and western blot analysis revealed that miR-217 negatively regulated KRAS protein expression, but had no impact on KRAS mRNA expression. Knockdown of KRAS expression markedly suppressed AML cellular proliferation, and enhanced cell chemosensitivity to doxorubicin via the cell apoptosis pathway. These findings indicate that miR-217 functions as a tumor suppressor in AML by directly targeting KRAS. Therefore, miR-217-based therapeutic strategies may provide a novel strategy for the enhancement of efficacy in the treatment of AML.

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MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism

Cited by 78 publications

References 42 publications

Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling

Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling

Long non-coding RNA GAS5 inhibits cell proliferation, induces G0/G1 arrest and apoptosis, and functions as a prognostic marker in colorectal cancer

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

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