Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

Torres, Anna; Torres, Kamil; Pesci, Anna; Ceccaroni, Marcello; Paszkowski, Tomasz; Cassandrini, Paola Agnese; Zamboni, Giuseppe; Maciejewski, Ryszard

doi:10.1186/1471-2407-12-369

Cited by 110 publications

(116 citation statements)

References 54 publications

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“…2). For example, miR-100 could suppress proliferation, induce apoptosis and cell cycle arrest in tumor cells by targeting multiple tumor-related genes such as mTOR, PI3K, AKT1, IGF1-R, HS3ST2, HOXA1, RAP1B, FGFR3, PIK1, Cyr61, FKBP51 [7,58,61,72,75,76,80,87,95]. Direct regulation of some oncogenes involved in tumor cell invasion and metastasis, such as HOXA1, Rac1, ICMT, EphB6, AGO2 by miR-100 has been identified in many cancers [32,41,67,96].…”

Section: The Functions Of Mir-100 and Its Target Genes In Human Cancersmentioning

confidence: 99%

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

Li¹,

Gao²,

Zhang³

et al. 2015

Cell Physiol Biochem

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MicroRNAs (miRNAs) are a recently discovered class of endogenous, small (about 22 nucleotides) non-coding RNAs, which play important roles in cancer development and progression. Emerging evidence shows that microRNAs exert their regulatory effects by directly binding to the 3'- untranslated regions (UTRs) of their target genes. MicroRNA-100 (miR-100) is aberrantly expressed and functions in many human cancers by regulating multiple cell processes, such as cell cycle, proliferation, differentiation, migration, invasion and apoptosis, via post-transcriptionally regulating various target genes. A better understanding of the molecular mechanisms involved in miR-100-mediated tumor progression will provide an opportunity for exploring novel miR-100-based targeted therapies for human cancers. This review aims to summarize the recently published literature on the roles of miR-100 in regulating tumorigenesis, and explore its potential clinical applications for cancer diagnosis, prognosis and clinical treatment.

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Section: The Functions Of Mir-100 and Its Target Genes In Human Cancersmentioning

confidence: 99%

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

Li¹,

Gao²,

Zhang³

et al. 2015

Cell Physiol Biochem

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“…MiR-99a is downregulated in several cancer cell lines and solid tumors including acute lymphoblastic leukemia, 34 hepatocellular carcinoma, 33 prostate cancer, 35 endometrioid endometrial cancer, 32 and lung cancer, 12 but the mechanisms responsible for its downregulation in tumors are still unknown. By overexpression or inhibition, researchers found that miR-99a could suppress cell proliferation, 35 induce G 1 -phase cell cycle arrest, 36 and promote apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Given previous reports showed that mTOR was a direct target of miR-99a in various cancers, 12,32,33 we tended to evaluate whether mTOR signaling was involved in D261-induced G 1 arrest. The predicted consequential pairing of target region of mTOR and miR-99a was shown in Figure 6C.…”

Section: Mir-99a/mtor Axis Is Involved In D261-regulated Cell Growth mentioning

confidence: 99%

A novel small-molecule compound diaporine A inhibits non-small cell lung cancer growth by regulating miR-99a/mTOR signaling

Song

Dou

Wang

et al. 2014

Cancer Biology & Therapy

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Abbreviations: NSCLC, non-small cell lung cancer; CDK, cyclin-dependent kinase; mTOR, mammalian target of rapamycin; p70S6K, ribosomal protein S6 kinase (70KD); CFSE, carboxyfluorescein diacetate succinimidyl ester; MK, midkine; miRNAs, microRNAsMicroRNas (miRNas) dysregulation is critically involved in lung cancer. Regulating miRNas by natural agents may be a new strategy for cancer treatment. We previously found that a novel small-molecule compound diaporine a (D261), a natural product of endophytic fungus 3lp-10, had potential anti-cancer activites. In the present study, the inhibitory effect of D261 on non-small cell lung cancer (NscLc) growth and its possible mechanisms involving miRNa regulation were investigated. By cell viability assay, cell proliferation analysis, and clonal growth assay, we proved that D261 effectively inhibited the proliferation of NscLc cells (NcI-h460 and a549) in vitro. administration of D261 (5 mg/kg) to NcI-h460 xenografts bearing mice also inhibited tumor growth and decreased the expression of cell proliferation regulator, midkine. Moreover, D261 induced cell cycle arrest with a reduced expression of various G 1 /s transition-related molecules including cyclin D1, cyclin e1, cDK4, and cDK2, but without influencing apoptosis in NscLc cells. Intriguingly, D261 modified expressions of some miRNas and especially upregulated miR-99a, whose direct target was mammalian target of rapamycin (mTOR). Furthermore, overexpression of miR-99a antagonized the anti-tumor actions of D261 including the suppression of mTOR pathway activation, cell cycle-related proteins and cell growth. In addition, blocking of miR-99a expression by transfection of miR-99a inhibitors before D261 treatment counteracted the anti-tumor effects of D261. These data suggest that miR-99a/mTOR pathway was involved in D261-induced tumor suppression in NscLc cells. D261 might be a potent anti-cancer agent by upregulating miR-99a expression.

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“…A combination of miR-199a and miR-542-3p can be used to diagnose endometriosis with a sensitivity of 96.61 % and specificity of 79.66 %, and this approach may serve as a noninvasive marker in practice . Torres et al (2012) found that expression of miR-99a, miR-100 and miR-199b was upregulated in serum of patients with endometrioid adenocarcinoma, and showed that a combination of miR-99a and miR-199b had a higher diagnostic value than each miRNA alone. Analysis of miRNAs in serum in a genome-wide study showed that a combination of four serum miRNAs, miR-222, miR-223, miR-186 and miR-204, can be used to diagnose endometrioid adenocarcinoma with high probability.…”

Section: Application Of Mirna In Endome-trial Cancer As a Biomarkermentioning

confidence: 99%

MicroRNAs in endometrial cancer

et al. 2013

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Endometrial cancer is a common malignant gynecological tumor, but there are few biomarkers that are useful for early and accurate diagnosis and few treatments other than surgery. However, use of microRNAs (miRNAs) that induces gene downregulation in cells may permit effective and minimally invasive diagnosis and treatment. In endometrial cancer cells, expression levels of miRNAs including miR-185, miR-210 and miR-423 are upregulated and those of miR-let7e, miR-30c and miR-221 are downregulated compared to normal tissues, and these miRNAs are involved in carcinogenesis, invasion and metastasis. miRNAs with expression changes such as miR-181b, miR-324-3p and miR-518b may be used as prognostic biomarkers and transfection of miR-152 may inhibit cancer growth. However, most current studies of miRNAs are at a basic level and further work is needed to establish clinical applications targeting miRNAs.

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Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma

Cited by 110 publications

References 54 publications

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

A novel small-molecule compound diaporine A inhibits non-small cell lung cancer growth by regulating miR-99a/mTOR signaling

MicroRNAs in endometrial cancer

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