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Adriamycin (doxorubicin) is an important traditional drug that exhibits cytotoxicity in Diffuse Large B-cell Lymphoma (DLBCL). Doxorubicin affects the DLBCL cells at all stages of their cell cycle. Combined with our previous results, this study discovered that the overexpression of hsa-miR-28-5p inhibited the proliferation, promoted apoptosis, and triggered cell cycle arrest at the S-phase in DLBCL cells. However, the effect of (Homo sapiens, hsa)-microRNA (miR)-28-5p on doxorubicin sensitivity in DLBCL has not been investigated. This study aims to reveal the effects of hsa-miR-28-5p on doxorubicin sensitivity at the level of DLBCL cells. Methods. To determine the optimal concentration of doxorubicin, different concentrations of doxorubicin were used to treat DLBCL cells. CCK-8 assay was used to detect the proliferation of DLBCL cells. The hsa-miR-28-5p-mimic NC and hsa-miR-28-5p mimic were transfected to doxorubicin-mediated DLBCL cells. Simultaneously, blank control groups were set up. The cells were cultured and transfected for 24\u2009h. Next, each group was administered with different concentrations of doxorubicin and cultured again for 24\u2009h to observe the effects of hsa-miR-28-5p on doxorubicin sensitivity at different times. The proliferation, early apoptosis, and late apoptosis in DLBCL cells were determined using soft agar colony-forming assay, mitochondrial membrane potential assay, and caspase-3 activity assay, respectively. The apoptosis and cell cycle were explored using Annexin V-PE\/7-AAD and PI\/RNase staining buffer, respectively. We speculated that PD-L1 might be involved in the effect of hsa-miR-28-5p on the sensitivity of adriamycin (doxorubicin) in the DLBCL cells. Hence, we performed immunohistochemistry (IHC) to determine PD-L1 expression within formalin-fixed paraffin-embedded (FFPE) samples from 52 DLBCL cases. Results. The optimal concentration of doxorubicin targeting DLBCL cells was found to be 3.028\u2009\u03bcmol\/l. The effect of doxorubicin on DLBCL cells was time- and concentration-dependent. hsa-miR-28-5p mimic\u2009+\u2009doxorubicin remarkably decreased proliferation of DLBCL. DLBCL cell apoptosis rate was the highest in hsa-miR-28-5p mimic\u2009+\u2009doxorubicin group. Apart from that, hsa-miR-28-5p mimic plus doxorubicin had the best effect in promoting DLBCL cell apoptosis. After the intervention of hsa-miR-28-5p mimic\u2009+\u2009doxorubicin on DLBCL cells, the cell cycle was arrested in the S-phase and DNA synthesis was blocked. hsa-miR-28-5p mimic\u2009+\u2009doxorubicin could regulate the cycle of DLBCL cells. As a result, overexpression of hsa-miR-28-5p combined with doxorubicin is possibly involved in the development of DLBCL by affecting the proliferation, apoptosis, and cycle of DLBCL cells. PD-L1 showed an association with the prognosis of DLBCL patients. Combining with the literature, this suggested hsa-miR-28-5p may influence DLBCL occurrence and therapeutic effect by regulating the PD-L1 level. Conclusion. The combination of hsa-miR-28-5p mimic and doxorubicin may be considered more effective in inhibiting growth, arresting the cell cycle, and promoting cell apoptosis of DLBCL cells compared to using doxorubicin alone. The effects of doxorubicin on DLBCL cells were found to be time- and concentration-dependent. The overexpression of hsa-miR-28-5p enhanced the effect of doxorubicin on DLBCL cells, which may be attributed to the regulation of PD-L1 levels.<\/jats:p>","DOI":"10.1155\/2022\/4290994","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T21:20:08Z","timestamp":1657747208000},"page":"1-14","source":"Crossref","is-referenced-by-count":6,"title":["Effects of hsa-miR-28-5p on Adriamycin Sensitivity in Diffuse Large B-Cell Lymphoma"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4408-0535","authenticated-orcid":true,"given":"Shufang","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Karamay Central Hospital, Karamay City 834000, The Xinjiang Uygur Autonomous Region of China, China"},{"name":"Department of Pathology, The Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Dongjie, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"},{"name":"Xinjiang Medical University, No. 567 North Shangde Road, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-7090","authenticated-orcid":true,"given":"Qinyu","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Karamay Central Hospital, Karamay City 834000, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2575-408X","authenticated-orcid":true,"given":"Haipeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology of Karamay Central Hospital, Number 67, Junggar Road, Karamay Region, Karamay 834000, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8631-4868","authenticated-orcid":true,"given":"Ken","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Karamay Central Hospital, Karamay City 834000, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0742-8072","authenticated-orcid":true,"given":"Xinxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Dongjie, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"},{"name":"Xinjiang Medical University, No. 567 North Shangde Road, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9762-6613","authenticated-orcid":true,"given":"Hongliang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Dongjie, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"},{"name":"Xinjiang Medical University, No. 567 North Shangde Road, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"},{"name":"Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan Southern Road, Urumqi 830054, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3016-2049","authenticated-orcid":true,"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Dongjie, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"},{"name":"Xinjiang Medical University, No. 567 North Shangde Road, Urumqi 830011, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-1964","authenticated-orcid":true,"given":"Mei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Emergency of Karamay Central Hospital, Number 67, Junggar Road, Karamay Region, Karamay 834000, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0519-779X","authenticated-orcid":true,"given":"Lixia","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology of Karamay Central Hospital, Number 67, Junggar Road, Karamay Region, Karamay 834000, The Xinjiang Uygur Autonomous Region of China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"S. 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