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The molecular events between activated mTOR and renal cysts\/AMLs are still largely unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The mouse model of TSC-associated renal cysts were constructed by knocking out\n                      <jats:italic>Tsc2<\/jats:italic>\n                      specifically in renal tubules (\n                      <jats:italic>Tsc2<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      ;\n                      <jats:italic>ksp-Cre<\/jats:italic>\n                      ). We further globally deleted PRAS40 in these mice to investigate the role of PRAS40.\n                      <jats:italic>Tsc2<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      cells were used as mTOR activation model cells. Inhibition of DNA methylation was used to increase miR-142-3p expression to examine the effects of miR-142-3p on PRAS40 expression and TSC-associated renal cysts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PRAS40, a component of mTOR complex 1, was overexpressed in\n                      <jats:italic>Tsc2<\/jats:italic>\n                      -deleted cell lines and mouse kidneys (\n                      <jats:italic>Tsc2<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      ;\n                      <jats:italic>ksp-Cre<\/jats:italic>\n                      ), which was decreased by mTOR inhibition. mTOR stimulated PRAS40 expression through suppression of miR-142-3p expression. Unleashed PRAS40 was critical to the proliferation of\n                      <jats:italic>Tsc2<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      cells and the renal cystogenesis of\n                      <jats:italic>Tsc2<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      ;\n                      <jats:italic>ksp-Cre<\/jats:italic>\n                      mice. In contrast, inhibition of DNA methylation increased miR-142-3p expression, decreased PRAS40 expression, and hindered cell proliferation and renal cystogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that mTOR activation caused by TSC2 deletion increases PRAS40 expression through miR-142-3p repression. PRAS40 depletion or the pharmacological induction of miR-142-3p expression impaired TSC2 deficiency-associated renal cystogenesis. Therefore, harnessing mTOR\/miR-142-3p\/PRAS40 signaling cascade may mitigate hyperactivated mTOR-related diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s11658-024-00638-x","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T06:02:34Z","timestamp":1727416954000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["mTOR\/miR-142-3p\/PRAS40 signaling cascade is critical for tuberous sclerosis complex-associated renal cystogenesis"],"prefix":"10.1186","volume":"29","author":[{"given":"Shuyun","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolai","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajid","family":"Jalal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxin","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongming","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8254-7664","authenticated-orcid":false,"given":"Lin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"638_CR1","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/s41568-018-0074-8","volume":"18","author":"D Mossmann","year":"2018","unstructured":"Mossmann D, Park S, Hall MN. mTOR signalling and cellular metabolism are mutual determinants in cancer. 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