{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:41:29Z","timestamp":1778542889313,"version":"3.51.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004054","name":"King Abdulaziz University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Acquired resistance is a major clinical challenge for tamoxifen-based therapy. In this study, we focused on lncRNA SNHG6 which plays a role in chemoresistance of cancer cells, but has never been investigated in the context of tamoxifen resistance. We found elevated levels of SNHG6 in tamoxifen-resistant estrogen receptor (ER)-positive MCF-7 cells (MCF7TR), relative to na\u00efve MCF-7 cells, as well as in tamoxifen-resistant T47D cells (T47DTR), relative to na\u00efve T47D cells, which correlated with induced vimentin, ZEB1\/2 and decreased e-cadherin, thus implicating a role of EMT in SNHG6-mediated tamoxifen resistance. Downregulation of SNHG6, using specific siRNA, sensitized MCF7TR as well as T47DTR cells to tamoxifen along with markedly reduced proliferation, invasion and anchorage-independent clonogenicity. Further, SNHG6 was found to sponge and inhibit miR-101 as the endogenous expression levels of SNHG6 and miR-101 inversely correlated in paired parental and tamoxifen-resistant cells and, moreover, silencing of SNHG6 in tamoxifen-resistant cells resulted in de-repression of miR-101, along with reversal of EMT. SNHG6 expression also directly correlated with increased stem cells markers Sox2, Oct4 and EZH2. miR-101 levels, manipulated by transfections with pre\/anti-miR-101 oligos, directly affected tamoxifen sensitivity of ER-positive cells with pre-miR-101 sensitizing MCF7TR and T47DTR cells to tamoxifen whereas anti-miR-101 inducing resistance of parental MCF-7 and T47D cells to tamoxifen. Further, miR-101 was found to attenuate SNHG6-mediated effects on tamoxifen resistance, EMT as well as stem cell markers, thereby making a case for SNHG6-miR-101 axis in tamoxifen resistance of ER-positive breast cancer cells. Thus, lncRNA SNHG6 is a novel modulator of tamoxifen resistance through its sponging of miR-101 and the resulting effects on EMT.<\/jats:p>","DOI":"10.3389\/fonc.2022.1015428","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T13:12:43Z","timestamp":1663938763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["LncRNA SNHG6 sponges miR-101 and induces tamoxifen resistance in breast cancer cells through induction of EMT"],"prefix":"10.3389","volume":"12","author":[{"given":"Mohammad 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