Elevated MiR-222-3p Promotes Proliferation and Invasion of Endometrial Carcinoma via Targeting ERα
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{"title"=>"Elevated miR-222-3p promotes proliferation and invasion of endometrial carcinoma via targeting ERα", "type"=>"journal", "authors"=>[{"first_name"=>"Binya", "last_name"=>"Liu", "scopus_author_id"=>"35082390700"}, {"first_name"=>"Qi", "last_name"=>"Che", "scopus_author_id"=>"55986292400"}, {"first_name"=>"Haifeng", "last_name"=>"Qiu", "scopus_author_id"=>"36187208700"}, {"first_name"=>"Wei", "last_name"=>"Bao", "scopus_author_id"=>"35387368700"}, {"first_name"=>"Xiaoyue", "last_name"=>"Chen", "scopus_author_id"=>"54379805500"}, {"first_name"=>"Wen", "last_name"=>"Lu", "scopus_author_id"=>"55252983900"}, {"first_name"=>"Bilan", "last_name"=>"Li", "scopus_author_id"=>"55581018500"}, {"first_name"=>"Xiaoping", "last_name"=>"Wan", "scopus_author_id"=>"55581084600"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24498137", "sgr"=>"84900310912", "scopus"=>"2-s2.0-84900310912", "doi"=>"10.1371/journal.pone.0087563", "pui"=>"373059554", "issn"=>"19326203"}, "id"=>"16687474-7d8d-3a85-8c7b-97547c7a3075", "abstract"=>"MicroRNAs play key roles in tumor proliferation and invasion. Here we show distinct expression of miR-222-3p between ERα-positive and ERα-negative endometrial carcinoma (EC) cell lines and primary tumors, and investigation of its relationship with ERα and other clinical parameters. In vitro, the function of miR-222-3p was examined in RL95-2 and AN3CA cell lines. MiR-222-3p expression was negatively correlated with ERα. Over-expressed miR-222-3p in RL95-2 cells promoted cell proliferation, enhanced invasiveness and induced a G1 to S phase shift in cell cycle. Furthermore, the miR-222-3p inhibitor decreased the activity of AN3CA cells to proliferate and invade. In vivo, down-regulated miR-222-3p of AN3CA cells inhibited EC tumor growth in a mouse xenograft model. Additionally, miR-222-3p increased raloxifene resistance through suppressing ERα expression in EC cells. In conclusion, miR-222-3p plays a significant role in the regulation of ERα expression and could be potential targets for restoring ERα expression and responding to antiestrogen therapy in a subset of ECs.", "link"=>"http://www.mendeley.com/research/elevated-mir2223p-promotes-proliferation-invasion-endometrial-carcinoma-via-targeting-er%CE%B1", "reader_count"=>9, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1370893"], "description"=>"<p>(A) ERα 3′ UTRs is a target of miR-222-3p. P3′UTR-ERα luciferase constructs, containing a wild type or mutated type ERα 3′ UTRs, were transfected into RL95-2 cells. Relative repression of firefly luciferase expression was standardized to a transfection control. The reporter assays were performed three times with essentially identical results. (B and C) MiR-222-3p and ERα levels were analyzed by qRT–PCR and western blot method, respectively. ERα levels decreased when miR-222-3p was upregulated in response to the miR-222m in RL95-2 cells, whereas the reverse was observed for ERα expression when miR-222-3p was knocked down in AN3CA cells. (D) The expression of pS2, cyclin D1 and PR was down regulated after miR-222m transfection in RL95-2 cell lines. Oppositely, in AN3CA cells, these ERα downstream genes were increased with miR-222-3p dampened. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "negatively", "regulates"], "article_id"=>921828, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.g004", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MiR_222_3p_negatively_regulates_ER_945_/921828", "title"=>"MiR-222-3p negatively regulates ERα.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370903"], "description"=>"<p>(A) Stable transfection of AN3CA cells with LV-miR-222i and LV-miR-222i NC. The percentage of transfected cells with fluorescence was >95%. (B) qRT-PCR analysis of miR-222-3p expression after transfecting with LV-miR-222i and LV-miR-222i NC in AN3CA cells. **** P<0.0001. (C) Tumor growth in nude mice. AN3CA cells with different treatment were injected subcutaneously into the interscapular area of nude mice. The short and long diameters of the tumors were measured weekly and tumor volumes (cm<sup>3</sup>) were calculated. *** P<0.001. (D) Weight of tumors in nude mice. **P<0.01 vs. either no transfection or control vector. (E) The nude mice with tumor formation and representative HE staining histopathologic image of tumor tissues in mice (upper panel, 200×). The expression of Ki67 and ERα in the tumor was detected by immunohistochemical techniques (200×).</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "assay", "nude"], "article_id"=>921833, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.g005", "stats"=>{"downloads"=>2, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tumorigenicity_assay_in_nude_mice_/921833", "title"=>"Tumorigenicity assay in nude mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370908"], "description"=>"<p>(A) Cell viability was significantly decreased in RL95-2 and AN3CA cells treated with raloxifene. A. Raloxifene (20-µM) induced 40% inhibition of cell viability after 48 h treatment. * P<0.05. (B and C) After 24 h transfection, cells were treated with 20-µM raloxifene. At next 24 h, 48 h and 72 h, cell viability was detected by MTT assay. With miR-222-3p increasing, the cell viability of RL95-2 cells was much higher, showing less sensitivity to raloxifene. In contrast, AN3CA cells became more sensitive after miR-222-3p being inhibited. *** P<0.001.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "raloxifene", "mir-222-3p", "rl95-2", "an3ca"], "article_id"=>921838, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.g006", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effects_of_raloxifene_and_miR_222_3p_on_RL95_2_and_AN3CA_cells_/921838", "title"=>"The effects of raloxifene and miR-222-3p on RL95-2 and AN3CA cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370909"], "description"=>"<p>Primers sequences for real-time PCR analysis.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "sequences", "Real-time", "pcr"], "article_id"=>921839, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.t002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primers_sequences_for_real_time_PCR_analysis_/921839", "title"=>"Primers sequences for real-time PCR analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370910"], "description"=>"<p>Characteristics of the endometrial carcinoma (EC) samples.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "endometrial", "carcinoma"], "article_id"=>921840, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.t001", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_the_endometrial_carcinoma_EC_samples_/921840", "title"=>"Characteristics of the endometrial carcinoma (EC) samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370916"], "description"=>"<div><p>MicroRNAs play key roles in tumor proliferation and invasion. Here we show distinct expression of miR-222-3p between ERα-positive and ERα-negative endometrial carcinoma (EC) cell lines and primary tumors, and investigation of its relationship with ERα and other clinical parameters. In vitro, the function of miR-222-3p was examined in RL95-2 and AN3CA cell lines. MiR-222-3p expression was negatively correlated with ERα. Over-expressed miR-222-3p in RL95-2 cells promoted cell proliferation, enhanced invasiveness and induced a G1 to S phase shift in cell cycle. Furthermore, the miR-222-3p inhibitor decreased the activity of AN3CA cells to proliferate and invade. In vivo, down-regulated miR-222-3p of AN3CA cells inhibited EC tumor growth in a mouse xenograft model. Additionally, miR-222-3p increased raloxifene resistance through suppressing ERα expression in EC cells. In conclusion, miR-222-3p plays a significant role in the regulation of ERα expression and could be potential targets for restoring ERα expression and responding to antiestrogen therapy in a subset of ECs.</p></div>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "mir-222-3p", "proliferation", "endometrial", "carcinoma", "targeting"], "article_id"=>921846, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563", "stats"=>{"downloads"=>9, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Elevated_MiR_222_3p_Promotes_Proliferation_and_Invasion_of_Endometrial_Carcinoma_via_Targeting_ER_945_/921846", "title"=>"Elevated MiR-222-3p Promotes Proliferation and Invasion of Endometrial Carcinoma via Targeting ERα", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370880"], "description"=>"<p>(A) MiR-222-3p expression level was much higher in ERα-negative ECs than in ERα-positive samples. (B, C and D) Expression of miR-222-3p across different grades, stages and nodal metastasis status. MiR-222-3p expression level was positively correlated with poor clinicopathological parameters. (E and F) MiR-222-3p and ERα expression were inversely related in ECs and normal endometrium tissues. These tissues were analyzed for miR-222-3p expression by TaqMan based qRT-PCR, followed by immunohistochemistry for ERα as described in “<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087563#s2\" target=\"_blank\">Materials and Methods</a>”. (G) Expression of miR-222-3p in cells with different ERα status. MCF-7 and RL95-2 cells were ERα-positive, while KLE and AN3CA cells were ERα-negative. Conversely, miR-222-3p expression was negative-related with ERα status. Bars are standard deviation (SD). The experiments were repeated three times. ** P<0.01 vs. RL95-2, MCF-7. ****P<0.0001 vs. RL95-2, KLE, AN3CA. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "mir-222-3p", "correlated", "clinicopathological", "endometrial"], "article_id"=>921815, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.g001", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_expression_of_miR_222_3p_correlated_with_ER_945_and_clinicopathological_parameters_in_endometrial_carcinoma_/921815", "title"=>"The expression of miR-222-3p correlated with ERα and clinicopathological parameters in endometrial carcinoma.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370886"], "description"=>"<p>(A) qRT-PCR in RL95-2 and AN3CA cells after enforced and silenced expression of miR-222-3p for 48 h. (B) Cells with different miR-222-3p expression level were assayed for proliferation by MTT method at various time points. (C) Overexpression of miR-222-3p led to a significant increase in anchorage-independent colony forming ability of RL95-2 cells. Colony formation (≥50 cells) was assessed using a colony counter. Knockdown of miR-222-3p led to a decrease in anchorage-independent colony forming ability of AN3CA cells. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "proliferation", "mir-222-3p"], "article_id"=>921821, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.g002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transfection_efficiency_and_cell_proliferation_after_miR_222_3p_expression_changes_/921821", "title"=>"Transfection efficiency and cell proliferation after miR-222-3p expression changes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/1370887"], "description"=>"<p>(A) MiR-222m-transfected RL95-2 cells and miR-222i-transfected AN3CA cells were subjected to fluorescence-activated cell sorting analysis, and the relative G1, S, and G2/M compartments calculated. Data represent the average percentage of cells in each compartment in three independent experiments, each performed in triplicate. (B) Representative photos and statistical plots of transwell assays in RL95-2 cells transfected with miR-222m and miR-222m NC, and AN3CA cells transfected with miR-222i and miR-222i NC (×100). More cells traversed the transwell membrane in miR-222m transfected cells, and fewer did so in the miR-222i transfected AN3CA cell line. To exclude the effect of cell proliferation, relative cell invasion ability of RL95-2 and AN3CA cells was analyzed by normalizing relevant invasive cell numbers to 48 h MTT OD values. The results in both cells showed that high level of miR-222-3p promoted the ability of relative cell invasion. (C) MMP-2 and MMP-9 decreased significantly in cells transfected with miR-222m and increased in miR-222i transfected cells. Data are expressed as mean±SD. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001.</p>", "links"=>[], "tags"=>["immunology", "Immunologic techniques", "Immunohistochemical analysis", "Molecular cell biology", "gene expression", "Obstetrics and gynecology", "Gynecologic cancers", "oncology", "Basic cancer research", "Tumor physiology", "Cancers and neoplasms", "Gynecological tumors", "Endometrial carcinoma", "women's health", "mir-222-3p", "secretion"], "article_id"=>921822, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Binya Liu", "Qi Che", "Haifeng Qiu", "Wei Bao", "Xiaoyue Chen", "Wen Lu", "Bilan Li", "Xiaoping Wan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087563.g003", "stats"=>{"downloads"=>1, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_miR_222_3p_on_cell_cycle_invasion_ability_and_secretion_of_MMPs_/921822", "title"=>"Effects of miR-222-3p on cell cycle, invasion ability and secretion of MMPs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 02:48:21"}

PMC Usage Stats | Further Information

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Relative Metric

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