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Review
. 2022 Oct;21(20):2121-2131.
doi: 10.1080/15384101.2022.2087755. Epub 2022 Jun 14.

Mir-34a: a regulatory hub with versatile functions that controls osteosarcoma networks

Zhimin Yang  1   2 , Tang Liu  1   2 , Xiaolei Ren  1   2 , Mei Yang  1   2 , Chao Tu  1   2 , Zhihong Li  1   2
Affiliations
Review

Mir-34a: a regulatory hub with versatile functions that controls osteosarcoma networks

Zhimin Yang et al. Cell Cycle. 2022 Oct.

Abstract

Osteosarcoma (OS) is one of the most prevalent and highly aggressive bone malignancies. The treatment strategies of OS is under standard regimens, including surgical resection, chemotherapy, and other adjuvant therapy. However, the 5-year survival rate is still unsatisfactory. Previous studies have demonstrated that the expression of miR-34a decreases in osteosarcoma, which is involved in regulating numerous genes directly or indirectly at the post-transcriptional level and other pathways. Thus, miR-34a plays an important role in mediating OS cell proliferation, differentiation, migration, and apoptosis, and might be a pivotal biomarker for OS with diagnostic and therapeutic potentials. In this review, we aim to summarize the relationship between miR-34a and OS, with an emphasis on the specific mechanisms in OS development referring to miR-34a. Moreover, the potential role of miR-34a as a diagnostic, prognostic, and therapeutic candidate for OS would be presented in detail. However, the molecular mechanisms related to miR-34a and OS remain elusive, and more investigations are needed to reach a comprehensive understanding.

Keywords: MiR-34a; diagnosis; osteosarcoma; prognoses; treatment.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Biogenesis and feedback loop of miR-34a. DNA damage induces the transcription of miR-34a by binding the promoter, CpG island. Firstly, miR-34a is transcribed as long hairpin molecule (pri-miRNA), which is processed by the human RNase Ill DROSHA to transform into pre-miRNAs. Then miR-34a is delivered into cytoplasm through Exportin-5 and subsequently is cut by another human RNaseIll, DICER. Lastly, the mature miR-34a strand generates after several steps and this mature strand is incorporated into the RNA-induced silencing complex (RISC). Like this, miR-34a could bind with the 3’-UTR of target mRNA, leading to the degradation or translation inhibition of mRNA. Besides, miR-34a could suppress SIRT1 to increase acetylation of p53, upregulating p53-dependent apoptosis.
Figure 2.
Figure 2.
MiR-34a is a core component in the regulation network of OS. MiR-34a regulated numerous downstream factors to directly or indirectly mediate apoptosis, proliferation, cell cycle arrest, migration, invasion and differentiation; the expression levels of miR-34a and its related targets could be interfered by a variety of lncRNAs, like SNHG7.
Figure 3.
Figure 3.
Combination therapy with doxorubicin and miR-34a/PAI-039. The detailed molecular mechanisms of the synergistic effects for OS were summarized in details. Doxorubicin and interference of miR-34a could inhibit oncogene expression and thereby suppress OS.
See this image and copyright information in PMC

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