**7. Conclusions**

*Antisense Therapy*

**48**

**miRNA** miR-409

miR-409-3p

miR-409-

Prostate cancer

Metastasis

Inhibits

Upregulation of Ras and

RSU1 and

Akt signaling

STAG2

promoter

3p/5p

miR-409-

Prostate cancer

Metastasis

Inhibits

Upregulation of Ras-ILK

STAG2 and

signaling

RSU1

promoter

3p/5p

miR-409-5p

**Table 2.**

*In vitro and in vivo validated miRNAs related to EMT, invasion, and metastasis that could represent future therapy targets.*

Breast cancer

Metastasis promoter

Inhibits RSU1

Upregulation of Ras signaling

Breast cancer

Metastasis inhibitor

Inhibits AKT1 p

Downregulation of PI3K-

AKT pathway

Inhibited breast cancer cell proliferation, migration, and invasion suppressed

tumor growth *in vivo*

Induces EMT in normal prostate

epithelia, promotes tumorigenicity and

stemness *in vivo*

Induction of an EMT phenotype,

decreased E-cadherin, increased

vimentin, b-actin and downregulation of

tumor suppressing genes

Induces proliferation and migration in cancer cells and tumor growth in mice

xenografts

NSCLC

Metastasis

Inhibits

Downregulation of

SPIN1-AKT signaling

inhibitor

SPIN1

**Pathology**

**Effect**

**Target**

**Mechanism**

**Effect** *in vitro* **and** *in vivo*

Inhibits cell growth, proliferation, and

migration *in vitro*; fewer lung metastatic

foci *in vivo*

**Clinical associations**

Downregulated in NSLC tissues,

correlated with tumor size, stage,

pleural invasion, and metastasis;

worse overall survival and disease-

free survival

Downregulated to a significant

[105]

extent in tumor samples, relative to

the corresponding nontumor tissues

Upregulated in human prostatic

[106]

tissues with higher Gleason score

and prostate cancer bone metastasis

Higher miR-409 expression in the

[107]

stromal fibroblasts, correlated with

higher Gleason score in prostatic

tissues

Upregulation in breast can

[108]

carcinoma tissues, correlated with

shorter survival

**Ref.**

[104]

miRNAs represent key modulators of the human genome because of their capacity to affect up to 60% of protein-coding genes. In cancer, genetic and epigenetic events lead to the alteration of miRNA expression and consequently their mRNA target genes. Functional studies have demonstrated that miRNA modulation in tumor cells causes changes in the phenotype, leading to increased apoptosis and cell death, suppression of tumor development, invasion, and metastasis by inhibiting the oncogenic miRNAs (oncomiRs) and/or substituting the deficient tumor suppressive miRNAs (TS-miRNAs). Considering the encouraging preclinical and clinical data, miRNA-based therapy could become a reliable tool in cancer management.
