{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:06:52Z","timestamp":1784639212915,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T00:00:00Z","timestamp":1585785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008549","name":"Shanxi Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>A major obstacle to effective cancer immunotherapy is the tumor immune microenvironment. Natural killer (NK) cell resistance has been suggested as a primary cause of poor prognosis in hepatocellular carcinoma (HCC), which seemingly correlates with CNOT7 overexpression. CNOT7, a cytoplasmic mRNA deadenylase that is highly expressed in HCC, may regulate cytokine transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) secretion by controlling nuclear factor\u2010\u03baB subunit p65 trafficking. CNOT7 depletion suppresses TGF\u2010\u03b21 secretion in HCC and promotes interferon\u2010\u03b3 (IFN\u2010\u03b3) secretion by NK cells, and we previously demonstrated that CNOT7 depletion reversed IFN\u2010\u03b3 resistance in HCC cells. Therefore, we hypothesized that CNOT7 depletion might reverse NK cell resistance by influencing the tumor immune microenvironment of HCC. To test this hypothesis, we examined the correlation between CNOT7, STAT1, TGF\u2010\u03b21 and IFN\u2010\u03b3 expression with hepatitis B virus\u2010related cirrhosis and HCC with hepatitis B virus\u2010related cirrhosis. We found that modulation of CNOT7 expression alters TGF\u2010\u03b21 secretion in HCC and IFN\u2010\u03b3 secretion in NK cells. We also examined the effects of NK cells in HepG2 cells with <jats:italic>CNOT7<\/jats:italic> knockdown, which showed that NK cell surface CD107a expression is up\u2010regulated and caspase\u20103 expression is significantly enhanced in CNOT7\u2010deficient HepG2 cells. Overall, our results show that knockdown of <jats:italic>CNOT7<\/jats:italic> expression reverses NK cell resistance in HCC cells. Therefore, CNOT7 depletion has potential as a new adjuvant therapy in immunotherapy for HCC.<\/jats:p>","DOI":"10.1002\/2211-5463.12836","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T17:26:49Z","timestamp":1583947609000},"page":"847-860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CNOT7 depletion reverses natural killer cell resistance by modulating the tumor immune microenvironment of hepatocellular carcinoma"],"prefix":"10.1002","volume":"10","author":[{"given":"Chongren","family":"Ren","sequence":"first","affiliation":[{"name":"Shanxi Bethune Hospital TaiYuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Ren","sequence":"additional","affiliation":[{"name":"Graduate College of Shanxi Medical University TaiYuan 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