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TMEM97 expression in CRC samples was analyzed by GEPIA and human protein atlas (HPA) databases. TMEM97, E\u2010cadherin, Vimentin, N\u2010cadherin, P\u2010glycoprotein (P\u2010gp), multidrug resistance\u2010associated protein 1 (MRP1)\/ABCC1, ABCC2, and the changes of protein kinase B\/mammalian target of rapamycin (mTOR) pathway were explored by western blot analysis. IC50 value for 5\u2010FU and cell viability was examined by MTT assay. Apoptosis was evaluated by flow cytometry. TMEM97 was highly expressed in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) based on GEPIA and HPA databases. TMEM97 knockdown attenuated 5\u2010FU resistance in HCT116\/R and SW480\/R cells, as evidenced by the reduced IC50 value for 5\u2010FU and the increased apoptosis. TMEM97 knockdown suppressed epithelial\u2010mesenchymal transition (EMT), expression of ATP\u2010binding cassette (ABC) transporters, and the Akt\/mTOR pathway. Mechanistically, activation of Akt\/mTOR pathway abolished the inhibitory effects of TMEM97 knockdown on 5\u2010FU resistance, EMT, and ABC transporter expression. In conclusion, TMEM97 knockdown inhibited 5\u2010FU resistance in CRC by regulating EMT and ABC transporter expression via inactivating the Akt\/mTOR pathway.<\/jats:p>","DOI":"10.1111\/cbdd.14490","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T02:30:20Z","timestamp":1708655420000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>TMEM97<\/scp> knockdown inhibits 5\u2010fluorouracil resistance by regulating epithelial\u2010mesenchymal transition and <scp>ABC<\/scp> transporter expression via inactivating the Akt\/<scp>mTOR<\/scp> pathway in 5\u2010fluorouracil\u2010resistant colorectal cancer cells"],"prefix":"10.1111","volume":"103","author":[{"given":"Yi","family":"Xu","sequence":"first","affiliation":[{"name":"Department of General Surgery Nanyang First People's Hospital  Nanyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanyang First People's Hospital  Nanyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery Nanyang First People's Hospital  Nanyang China"},{"name":"Nanyang Key Laboratory of Thyroid Tumor Prevention and Treatment, Nanyang First People's Hospital  Nanyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery The Fourth Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065\u2010230X(05)94002\u20105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2011.08235.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(10)60353\u20104"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2003.07.007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.12.042"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2005.03.8323"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clcc.2014.11.002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277\u2010012\u20100612\u2010z"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3669"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.19079"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2009.12.008"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.17.1.615"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.14670\/hh\u201019.1021"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.5487\/tr.2015.31.2.151"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612829666230614154847"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.3.839"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.03.027"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010009\u20109194\u20107"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012864.pub2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soc.2017.11.008"},{"issue":"1","key":"e_1_2_8_24_1","first-page":"91","article-title":"Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers","volume":"30","author":"Moparthi S. 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