{"id":{"repo_id":"siu-theses","oai_identifier":"oai:opensiuc.lib.siu.edu:dissertations-1206"},"canonical_url":"https://search.dev.ndltd.org/etd/siu-theses/oai:opensiuc.lib.siu.edu:dissertations-1206","repository":{"repo_id":"siu-theses","name":"Southern Illinois University","base_url":"https://opensiuc.lib.siu.edu/do/oai/"},"display":{"title":"MiR-145 is a tumor suppressor in both tumor progression and metastasis","abstract":"MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level by interacting with the 3'-untranslated region (3'-UTR) of a target gene. Our previous studies indicate that miR-145 is downregulated in breast and colon cancer; moreover, it functions as a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that a putative tumor suppressor, miR-145, is regulated through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145. Although miR-145 silences the expression of c-Myc, anti-miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145- mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti-miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53. in addition, we show that miR-145 exerts its growth inhibitory function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis.","abstract_html":"MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level by interacting with the 3'-untranslated region (3'-UTR) of a target gene. Our previous studies indicate that miR-145 is downregulated in breast and colon cancer; moreover, it functions as a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that a putative tumor suppressor, miR-145, is regulated through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145. Although miR-145 silences the expression of c-Myc, anti-miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145- mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti-miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53. in addition, we show that miR-145 exerts its growth inhibitory function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis.","abstract_has_math":false,"creators":["SACHDEVA, MOHIT"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Campus Only Dissertation","degree_discipline":"Molecular Biology, Microbiology and Biochemistry","degree_department":null,"school":null,"contributors":["Mo, Yin"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-12-01T08:00:00Z","date_published":"2010-12-01T08:00:00Z","updated_at":"2026-07-24T04:33:31Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://opensiuc.lib.siu.edu/dissertations/206","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Mo, Yin"]},{"key":"dc:creator","label":"Author","values":["SACHDEVA, MOHIT"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular Biology, Microbiology and Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Campus Only Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://opensiuc.lib.siu.edu/dissertations/206"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level by interacting with the 3'-untranslated region (3'-UTR) of a target gene. Our previous studies indicate that miR-145 is downregulated in breast and colon cancer; moreover, it functions as a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that a putative tumor suppressor, miR-145, is regulated through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145. Although miR-145 silences the expression of c-Myc, anti-miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145- mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti-miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53. in addition, we show that miR-145 exerts its growth inhibitory function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis."]},{"key":"dc:title","label":"Title","values":["MiR-145 is a tumor suppressor in both tumor progression and metastasis"]}]}],"canonical_facts":{"dc:contributor":["Mo, Yin"],"dc:creator":["SACHDEVA, MOHIT"],"dc:description.abstract":["MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression at the post-transcriptional level by interacting with the 3'-untranslated region (3'-UTR) of a target gene. Our previous studies indicate that miR-145 is downregulated in breast and colon cancer; moreover, it functions as a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that a putative tumor suppressor, miR-145, is regulated through the phosphoinositide-3 kinase (PI-3K)/Akt and p53 pathways. Importantly, p53 transcriptionally induces the expression of miR-145 by interacting with a potential p53 response element (p53RE) in the miR-145 promoter. We further show that c-Myc is a direct target for miR-145. Although miR-145 silences the expression of c-Myc, anti-miR-145 enhances its expression. This specific silencing of c-Myc by miR-145 accounts at least in part for the miR-145- mediated inhibition of tumor cell growth both in vitro and in vivo. Finally, the blockade of miR-145 by anti-miR-145 is able to reverse the p53-mediated c-Myc repression. Together, these results define the role of miR-145 in the posttranscriptional regulation of c-Myc by p53. in addition, we show that miR-145 exerts its growth inhibitory function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis."],"dc:identifier":["https://opensiuc.lib.siu.edu/dissertations/206"],"dc:title":["MiR-145 is a tumor suppressor in both tumor progression and metastasis"],"thesis:degree_discipline":["Molecular Biology, Microbiology and Biochemistry"],"thesis:degree_level":["Campus Only Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T04:33:31Z"}