Mechanisms involved in the HMGB1 modulation of tumor multidrug resistance (Review)

Abstract

Tumor multidrug resistance (MDR) remains one of the most challenging barriers to successful cancer treatment. Several previous studies have suggested that high mobility group box 1 (HMGB1) may be a promising therapeutic target for overcoming cancer drug resistance. Emerging evidence has indicated that HMGB1 functions as a 'double‑edged sword' that plays both pro‑ and anti‑tumor roles in the development and progression of multiple types of cancer. HMGB1 has also been found to be a key regulator of several cell death and signaling pathways, and is involved in MDR by mediating cell autophagy and apoptosis, ferroptosis, pyroptosis and multiple signaling pathways. Additionally, HMGB1 is regulated by a variety of non‑coding RNAs (ncRNAs), such as microRNAs, long ncRNAs and circular RNAs that are involved in MDR. Thus far, studies have been conducted to identify strategies with which to overcome HMGB1‑mediated MDR by the targeted silencing of HMGB1 and the targeted interference of HMGB1 expression using drugs and ncRNAs. Therefore, HMGB1 is closely associated with tumor MDR and is a promising therapeutic target.

Keywords: apoptosis and autophagy; ferroptosis; high mobility group box 1; nanoparticles; non‑coding RNA; pyroptosis; traditional Chinese medicine; tumor multidrug resistance.

Figure 1

Mechanistic diagram of the roles of HMGB1 in MDR. HMGB1 regulates DNA damage repair and genome stability in the nucleus. In the cytoplasm, HMGB1 increases autophagy, inhibits apoptosis and plays a regulatory role in mitochondrial functions, regulating ferroptosis and pyroptosis, thereby mediating MDR. Extracellular HMGB1 can regulate multiple signaling pathways and induce downstream biological effects, thereby mediating drug resistance. A variety of ncRNAs can regulate the expression of HMGB1 and promote MDR. HMGB1, high mobility group box 1; MDR, multidrug resistance; ncRNA, non-coding RNA; mTOR, mammalian target of rapamycin.