Dysregulation of miR-15a and miR-214 in human pancreatic cancer

Zhang, Xing J; Ye, Hua; Zeng, Chengwu; He, Bo; Zhang, Hua; Chen, Yue Q

doi:10.1186/1756-8722-3-46

Cited by 183 publications

(168 citation statements)

References 32 publications

(27 reference statements)

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“…Recent evidence has suggested that miRNAs may be involved in the progression of human cancer, since numerous miRNAs have been observed to be deregulated during tumorigenesis in humans (19). Previous studies have demonstrated that miR-214 is downregulated in cervical cancer and upregulated in human pancreatic cancer (20,21). The present study has demonstrated that the expression of miR-214 was downregulated in HCC tissues and cell lines.…”

Section: Discussionsupporting

confidence: 63%

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

Yang¹,

Chang²,

Zhao³

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are important gene regulators that participate in tumorigenesis. Previous studies have implicated that miR-214 is a tumor suppressor that is capable of inhibiting human hepatocellular carcinoma (HCC) cell growth. However, the mechanism by which miR-214 suppresses tumor development remains unknown. In the present study, miR-214 was observed to suppress tumor proliferation by directly targeting E2F transcription factor 3 (E2F3) in HCC cells. Colony formation, cell cycle and proliferation assays were employed to study the tumor suppressor role of miR-214 in cell proliferation. In addition, western blotting and dual-luciferase reporter assays were used to evaluate whether E2F3 was a target of miR-214. The results of these analyses revealed that E2F3 was a novel target of miR-214. Furthermore, enhanced expression of miR-214 or silencing of E2F3 inhibited the proliferation of HCC SMMC-7721 cells. These findings suggest that miR-214 suppresses HCC growth by targeting E2F3, and may provide a novel approach for the treatment of human HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most common types of malignancy and the third leading cause of cancer-associated mortalities worldwide, due to its poor prognosis and frequent relapse and metastasis (1,2). Furthermore, HCC is difficult to treat, since it is usually diagnosed at advanced stages (3). Thus, studying the molecular mechanism of HCC in order to identify novel prognostic markers or therapeutic targets for the treatment of HCC is of value.MicroRNAs (miRNAs) are small noncoding RNAs of ~22 nucleotides (nt) in length that regulate gene expression at the post-transcriptional level (4). miRNAs are initially transcribed as long primary precursor molecules named pri-miRNAs, which are processed in a number of endonuclease reactions to produce the mature effector 22-nt miRNA molecule (5). Through the specific targeting of the 3'-untranslated regions (3'-UTRs) in the target genes of the miRNA, the translational repression and degradation of their target mRNA occurs (6). By targeting various transcripts, miRNAs are involved in a number of fundamental biological processes, including cell proliferation and differentiation, apoptosis, development and metabolism (7-9). Previous studies suggest that the expression of miRNAs is remarkably dysregulated in cancer, due to numerous epigenetic and genomic alterations (10,11). Several miRNAs have been demonstrated to act as tumor suppressor genes or oncogenes in tumors (12). As one miRNA may potentially regulate numerous mRNAs, it is clear that they are important regulatory molecules. Consistently, previous studies have considered miRNAs as important biomarkers and promising therapeutic targets for the treatment of various diseases (13). Recently, miR-214 was reported to be involved in certain types of cancer, including breast (14), adrenocortical (15), ovarian (16) and gastric cancer (17). Thus, the roles of miR-214 may be critical in the development of cancer.In the present study, bioinformatics...

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Section: Discussionsupporting

confidence: 63%

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

Yang¹,

Chang²,

Zhao³

et al. 2015

Oncology Letters

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“…It has been documented to be aberrantly expressed in many tumors including breast, cervical, hepablastoma, pancreatic and lung cancer (Yanaihara et al, 2006;Magrelli et al, 2009;Yang et al, 2009;Zhang et al, 2010Derfoul et al, 2011. Accumulating evidence indicated that miR-214 functions either as onco-gene or tumor suppressor gene in different tumors.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-214 Regulates the Acquired Resistance to Gefitinib via the PTEN/AKT Pathway in EGFR-mutant Cell Lines

Wang¹,

Wang²,

Xia³

et al. 2012

Asian Pacific Journal of Cancer Prevention

105

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Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/ GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

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“…For example, miR-214 has been shown to be upregulated in ovarian cancer (18), gastric cancer (19), Sézary syndrome (20) and melanoma (15), while it has been shown to be downregulated in cervical cancer (21), pancreatic cancer (22) and hepatocellular carcinoma (23). A recent study found that the concentrations of miR-214 were significantly higher in the serum of breast cancer patients in contrast to healthy women (24).…”

Section: Introductionmentioning

confidence: 99%

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

Wang

et al. 2015

International Journal of Molecular Medicine

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Abstract. Breast cancer (BC) is the foremost cause of cancerrelated mortality in women worldwide. An increasing number of studies has confirmed that microRNAs (miRNAs or miRs) play an important role in the development and progression of BC. microRNA-214 (miR-214), a member of the miRNA family, has been demonstrated to function as both a tumor suppressor and oncogene in various types of human cancer. However, the biological function of miR-214 in BC remains unclear. The present study was designed to investigate the potential role of miR-214 in the development and progression of BC. Our results revealed that miR-214 expression was significantly increased in the BC tissues compared with the adjacent benign tissues, and that the upregulation of miR-214 was significantly associated with the invasion ability of the BC cells. Furthermore, p53, which has been reported to be downregulated in BC, was predicted to be the target gene of miR-214 using bioinformatics software programs. Moreover, luciferase reporter vectors were constructed and it was confirmed that p53 is a target of miR-214. Following the transfection of miR-214 into BC cells, we found that the overexpression of miR-214 markedly enhanced cell invasion through the downregulation of p53 expression. By contrast, the overexpression of p53 abrogated the effects of miR-214. In conclusion, this study demonstrates that miR-214 functions as an oncogene in BC, at least partly by promoting cell invasion through the downregulation of p53. Therefore, miR-214 may be a potential therapeutic target for the treatment of BC.

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Dysregulation of miR-15a and miR-214 in human pancreatic cancer

Cited by 183 publications

References 32 publications

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

MicroRNA-214 Regulates the Acquired Resistance to Gefitinib via the PTEN/AKT Pathway in EGFR-mutant Cell Lines

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

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