title: HMGB1 knockdown effectively inhibits the progression of rectal cancer by suppressing HMGB1 expression and promoting apoptosis of rectal cancer cells.
abstract: Rectal cancer is a malignant gastrointestinal tumor, which is associated with high morbidity and mortality. High‑mobility group protein 1 (HMGB1) is widely present in the nucleus of eukaryotic cells, and is highly conserved between humans and rodents. Recently, HMGB1 has been reported to be involved in the progression and metastasis of human cancer; however, its role in the development and metastasis of human rectal cancer remains unclear. The present study detected the expression levels of HMGB1 in pathological specimens from patients with clinically identified rectal cancer using immunohistochemistry and western blotting. The results demonstrated that HMGB1 was highly expressed in samples from patients with rectal cancer. The positive rate of HMGB1 in rectal cancer tissues was 96.08% (49/51), which was significantly higher compared with 3.92% (2/51) in normal tissues. In addition, western blotting indicated that HMGB1 was distributed and located not only in the nucleus, but also in the cytoplasm of colorectal cancer cells. HMGB1‑specific short hairpin (sh)RNA was used to silence the endogenous expression of HMGB1 in colorectal cancer cells. A functional assay demonstrated that knockdown of endogenous HMGB1 expression significantly inhibited the proliferation of SW620 and Colo320 cells. Furthermore, western blotting revealed that knockdown of endogenous HMGB1 expression contributed to activation of caspase‑3 and the substrate poly (ADP‑ribose) polymerase. The expression levels of B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) were also detected by western blotting. As expected, decreased levels of Bcl‑2 and increased levels of Bax were detected in the HMGB1 shRNA‑transfected colorectal cancer cells, and the Bax/Bcl‑2 ratio was increased in HMGB1 shRNA‑transfected cells. These data indicated that HMGB1 may act as an oncogene in rectal cancer, and knockdown of endogenous HMGB1 expression may significantly inhibit the proliferation of colorectal cancer cells and promote apoptosis of tumor cells. Further research regarding the mechanisms underlying the effects of HMGB1 on the progression of rectal cancer may provide novel targets for the treatment of rectal cancer, and provide a theoretical reference for clinical treatment.
authors.affiliation: Qingdao Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Healthcare Ward, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China.
authors.forename: Jiantian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Qingdao Medical College, Qingdao University, Qingdao, Shandong 266042, P.R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China.
authors.forename: Ruiyun
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal and Anorectal Surgery, Qingdao Central Medical Group, Qingdao, Shandong 266042, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D024243:HMGB1 Protein; D034741:RNA, Small Interfering; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3