Recently, microRNAs (miRNAs) including miR-34 family have been found to play a critical role in tumorigenesis through regulating the expression of its target genes, which are involved in many cellular processes such as cell proliferation, survival, apoptosis, migration, invasion and angiogenesis.
Finally, miR-34 reconstitution experiments in p53 mutant EOC cells resulted in reduced proliferation, motility, and invasion, the latter of which was dependent on MET expression.
In our study, RIG-I and miR-34a suppressed cell growth, proliferation, migration, and invasion in cervical cancer cells in vitro. miR-34a was validated as a new regulator of RIG-I by binding to its 3' untranslated region and upregulating its expression level.
Overexpression of c-Myc reversed miR-34a suppression of RhoA expression and inhibition of cell invasion, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to repress the c-Myc-P-TEFb transcription elongation complex, indicating one of the mechanisms by which miR-34a has profound effects on cellular functions.
Through gain- and loss-of-function studies, miR-34a was demonstrated to negatively regulate CXCL10; inhibit activation of the TLR signaling pathway; significantly suppress in vitro cell proliferation, migration, and invasion; and induce apoptosis.
The low expression of miR-34a in patients with cervical cancer is related to the degree of tumor differentiation as well as invasion and metastasis, and the low expression of miR-218 is related to the degree of tumor differentiation, invasion and metastasis and clinical staging. miR-34a and miR-218 in the serum can be used as markers for the diagnosis of cervical cancer and reference indicators for the evaluation of prognosis.
Consistent with these observations, we demonstrated a functional tumor suppressive role for miR-34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar.
We identified several miR-34a target genes, including Arhgap1, which encodes a RHO GTPase activating protein that was required for tumor cell invasion.
Decreased expression of long non-coding RNA SNHG7 cause recurrent spontaneous abortion through suppression proliferation and invasion of trophoblast cells via miR-34a.
In functional experiments, miR-34a mimic suppressed cell growth, migration and invasion, meanwhile it increased cellular apoptosis and caspase activity in HCC cells. miR-34a mimic also reduced phospho-ERK1/2 and phospho-stat5 signaling.
Functional characterization of miR-34a was accomplished by reconstitution of miR-34a expression in ovarian cancer cells by determining changes in proliferation, migration, and invasion.
T-VISA-miR-34a induced robust, persistent expression of miR-34a, and dramatically suppressed breast cancer cell growth, migration, and invasion in vitro by downregulating the protein expression levels of the miR-34a target genes E2F3, CD44, and SIRT1.
While forced expression of miR-34a in CaCx and CRC cells inhibited HMGB1 mRNA and protein levels, proliferation, migration and invasion, inhibition of endogenous miR-34a enhanced these tumourigenic properties. siRNA-mediated HMGB1 suppression imitated miR-34a expression in reducing proliferation and metastasis-related events.
The results indicated that miR‑34a was downregulated in the gastric cancer tissues, compared with the normal gastric tissues (P<0.01). miR‑34a was negatively correlated with the depth of invasion and lymph node metastasis of gastric cancer (P<0.01).
Using a panel of canine OSA cell lines, we found that tRNA/miR-34a reduced viability, clonogenic growth, and migration and invasion while increasing tumor cell apoptosis.