High‐mobility group box 2 promoted proliferation of cervical cancer cells by activating AKT signaling pathway

Abstract

Cervical cancer is one of the leading killers for female worldwide. Nevertheless, the less knowledge of molecular mechanism for cervical cancer limited the improvement of treatment effects. High‐mobility group box 2 (HMGB2) belongs to the HMGB family, which could play diverse roles in cell proliferation. This work mainly aimed to study the functions of HMGB2 on cervical cancer cells proliferation. HMGB2 was highly expressed in cervical cancer tissue. The results of real‐time polymerase chain reaction and Western blot analysis showed that HMGB2 was expressed in all the five cervical cancer cells (HeLa, CaSki, SiHa, C‐33A, and C4‐1 cells). In addition, HMGB2 overexpression obviously improved cell viability and promoted cell cycle progression, which suggested that HMGB2 could promote proliferation of cervical cancer cells. Moreover, HMGB2 overexpression increased the level of p‐AKT and reduced the levels of p21 and p27. However, HMGB2 downregulation had contrary influences on cell proliferation, cell cycle distribution and the levels of p‐AKT, p21, and p27. Notably, LY294002, as an inhibitor of AKT signaling pathway, could significantly weaken the effects of HMGB2 overexpression, which indicated that HMGB2 might promote cell proliferation by activating AKT signaling pathway. Therefore, HMGB2 was hopeful to be a candidate as a new biomarker and therapy target for cervical cancer.

Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19

“…TF prediction pointed to members of the E2F family as key TFs, further emphasizing the proliferative functionality of these genes. HMGB2, a factor related to cell proliferation in cancer (Zhang et al, 2019b), was predicted as the top potential ligand. Module 4 was enriched in genes specifically upregulated in week 1 in severe COVID-19 NK cells.…”

Biological functions and theranostic potential of HMGB family members in human cancers

“…82 HMGB2 can also activate the AKT pathway by phosphorylating AKT and suppress the expression of p21 and p27 in cervical cancer. 83 cytoplasmic maintenance of HMGB2 and inhibits downstream EMT signaling. 74 To put it another way, HMGB2-mediated EMT could lead to metastasis.…”

“…82 HMGB2 can also activate the AKT pathway by phosphorylating AKT and suppress the expression of p21 and p27 in cervical cancer. 83 This suggests that AKT and Wnt pathways are closely associated with HMGB2-mediated proliferation of cancer.…”

Identification of differentially expressed proteins and clinicopathological significance of HMGB2 in cervical cancer

“…Lately, HMGB2 has been found to overexpress and promote cell proliferation and radiosensitivity through retinoblastoma-interaction-dependent or independent mechanisms [38]. Our recent research revealed that, according to the RNA-Seq data from The Cancer Genome Atlas (TCGA) program and The Genotype-Tissue Expression (GTEx) project, HMGB2 expression was significantly higher in cervical squamous cell carcinoma and endocervical adenocarcinoma than that in the normal controls; up-regulated HMGB2 expression promoted cell proliferation by activating AKT signaling pathway in cervical cancer cell lines [39]. Additionally, high expression of HMGB2 was associated with a poor prognosis for the patients with breast cancer via promoting cell proliferation and glycolysis in breast cancer cells [40,41].…”