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

Figures & data

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.

Table 1. Abnormal expression of the MiR-34a in various cancers.

tumor type	expression level compared with normal tissues	Reference
neuroblastoma	down	[86]
glioma	down	[87]
head and neck squamous cell carcinoma	up	[88]
Medullary thyroid carcinoma	up	[89]
Esophageal squamous cell carcinoma	down	[90]
non-small cell lung cancer	down	[91]
small cell lung cancer	down	[92]
ovarian cancer	down	[93]
breast cancer	down	[94]
ovarian cancer	down	[95]
prostate cancer	down	[96]
bladder cancer	up	[97]
hepatocellular carcinoma	down	[98]
clear cell renal cell carcinoma	up	[99]
colon cancer	down	[100]
colon cancer	down	[101]
osteosarcoma	down	[18]

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. 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.

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