Cancer Management and Research (Nov 2021)

Exosomal miR-122-5p is Related to the Degree of Myelosuppression Caused by Chemotherapy in Patients with Colorectal Cancer

  • Chen J,
  • Wu W,
  • He X,
  • Jia L,
  • Yang J,
  • Si X,
  • Yu K,
  • Li S,
  • Qiu Y,
  • Xu K,
  • Yin P,
  • Cao Y,
  • Li Q,
  • Li W

Journal volume & issue
Vol. Volume 13
pp. 8329 – 8339

Abstract

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Jinbao Chen,1,* Wentao Wu,1,* Xue He,1 Linlin Jia,1 Jiahua Yang,1 Xianke Si,1 Kun Yu,1 Sen Li,1 Yanyan Qiu,1 Ke Xu,2 Peihao Yin,1,3 Yijun Cao,1 Qiong Li,4 Wei Li1 1Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China; 3Interventional Cancer Institute of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei LiDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional, Chinese Medicine, Shanghai, 200062, People’s Republic of ChinaEmail [email protected] LiDepartment of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201100, People’s Republic of ChinaEmail [email protected]: As rapidly dividing cells are usually the target of anticancer chemotherapy, it is inevitable that rapidly dividing normal cells become damaged, with myelosuppressive effects being a serious side effect of this therapy. Many recent studies have found that exosomal microRNAs (miRNAs) are related to the occurrence of some diseases.Patients and Methods: Small RNA sequencing was used to investigate differential exosomal miRNAs with the same expression trend between groups after chemotherapy: MildA (before chemotherapy in patients with mild myelosuppression) and MildB (after chemotherapy in patients with mild myelosuppression); SevereA (before chemotherapy in patients with severe myelosuppression) and SevereB (after chemotherapy in patients with severe myelosuppression). A Venn diagram was generated to screen exosomal miRNAs related to chemotherapy. Small RNA sequencing was also used to investigate differentially expressed exosomal miRNAs among these groups, and exosomal miRNAs related to myelosuppression after chemotherapy was explored using a Venn diagram. RT-qPCR was applied to further verify the sequencing results. We performed target gene prediction and functional analysis for candidate exosomal miRNAs.Results: Compared with that in the MildA or SevereA group, an increase in exosomal miR-122-5p was found in the MildB or SevereB group, and the expression level was lower in the SevereB group than in the MildB group. However, we found no notable difference in its expression level between the MildA and SevereA groups. Similar results were not obtained for the remaining miRNAs. RT-qPCR confirmed the screening results. Further analyses indicated that exosomal miR-122-5p targets CDK4 to inhibit the cell cycle.Conclusion: The expression level of exosomal miR-122-5p in the serum of patients with colorectal cancer correlates with the severity of myelosuppression caused by chemotherapy, and miR-122-5p targets CDK4 to inhibit cell cycle progression.Keywords: colorectal cancer, chemotherapy, myelosuppression, miR-122-5p

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