miR-361 expression

We found for the first time that plasma exosomal miR-361-3p was associated with malignant progression in BC patients. Mechanistically, exosomal miR-361-3p can enhance the migration and proliferation of BC cells by targeting the ETV7 and BATF2/PAI-1/ERK pathways. Our data suggest that plasma exosomal miR-361-3p has the potential to serve as a biomarker for predicting malignant progression in BC patients.

Downregulation of miR-361-3p along the Gli1 axis promoted tumor malignancy. Collectively, the results of this study imply that miR-361-3p has the potential to be both a biomarker and therapeutic target in PCa.

In addition, we noted that the tissue surrounding the tumor in patients with distant metastases showed a significantly higher expression of miR-3613-3p compared to patients without distant metastases. The increased expression of miR-3613-3p in patients after radiotherapy suggests the possibility of using this miR as a therapeutic target for CRC, but this requires confirmation in further studies.

Finally, the over-expression of KMT2A partially reversed the inhibitory effects of up-regulation of miR-361-3p. A potential therapeutic candidate target for the treatment of AML may be miR-361-3p/KMT2A.

The positive correlation between WT1 with MDA and TOS and negative correlation between TAC and miR-361-5p suggests that this gene can play an important role in worse prognoses in breast cancer. Additionally, miR-361-5p may serve as an invasive biomarker for early detection of breast cancer.

MiR-3612 retarded NPC cell migration, adhesion, and proliferation by targeting THBS1 and inactivating the PI3K/AKT signaling pathway. This provides a novel therapeutic approach for NPC intervention.

BBOX1-AS1 facilitated the EC development and malignancy via miR-361-3p/COL1A1 axis, indicating BBOX1-AS1 could be a novel therapy target on the diagnostic of EC.

Importantly, luciferase reporter assays further verified that miR-3614-5p suppressed the expression of TXNRD1 by directly binding to the 3'-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614-5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.

RT-qPCR and Western blotting confirmed that LINC00992 upregulated the expression of the Twist1 gene in HCC cells by downregulating expression of miR-361-5p. CCK-8 and Transwell assays confirmed that LINC00992 promoted the proliferation, metastasis, and invasiveness of HCC cells by downregulating miR-361-5p levels and consequently upregulating Twist1 expression, implying that these three elements may be promising targets for HCC therapy.

MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.

Rh2 inhibits CFAP20DC-AS1, which obscures the association of the lncRNA with miR-3614-3p, resulting in the suppression of oncogenic BBX and TNFAIP3. Taken together, the Rh2/CFAP20DC-AS1/miR-3614-3p/target gene axis contributes to the antiproliferation activity of Rh2 in cancer cells.

Besides, in vivo assays revealed that miR-361-3p overexpression facilitated tumor growth in nude mice. In conclusion, this study indicates that miR-361-3p is a crucial prognostic biomarker of osteosarcoma, and that targeting of miR-361-3p/ARID3A axis may be a promising strategy in osteosarcoma therapy.

In PC cells, overexpression of MAPK/JNK diminished the pro-apoptotic effect of the miR-361 mimic, while restoring the migratory activity of PC cells. Collectively, the present results suggested novel molecular mechanisms underlying PC progression and development.

Advanced studies demonstrated that hsa_circ_0000006 regulates LRIG1 expression through sponging miR-361-3p, then promotes the tumorigenesis of OS. hsa_circ_0000006 is associated with the progression and development of OS through miR-361-3p by target LRIG1, which is a significant biomarker and effective therapeutic target for patients with OS.

miR-361 is potentially functioning as a potent marker for HBV-relevant HCC development or liver fibrosis (LF) progression.

RNA pull-down assay and luciferase reporter gene assay confirmed the binding between circGFRA1 and miR-361-5p and between miR-361-5p and TLR4. It has been proven that circGFRA1 knockdown can inhibit the resistance of TNBC cells to PTX by promoting the expression of miR-361-5p, and subsequently reduce the expression of TLR4.

Overexpression of circRNA_000864 or downregulation of miR-361-3p also decreased the tumor growth in vivo. Conjointly, our findings elicited that the overexpression of circRNA_000864 could promote BTG2 expression to inhibit pancreatic cancer development by binding to miR-361-3p, which represents an appealing therapeutic target for the treatment of pancreatic cancer.

Following SNHG22 or HMGA1 silencing or miR-361-3p upregulation, we observed a decline of proliferation, migration, and invasion of GC cells and HUVEC angiogenesis but acceleration of GC cell apoptosis and cell cycle arrest. Collectively, SNHG22 silencing possessed tumor-suppressing potentials in GC development via Wnt/β-catenin pathway by binding to miR-361-3p and downregulating HMGA1, highlighting a new promising road for GC treatment development.

Our findings suggested that miR-3613-3p acts as a cancer-suppressor miRNA in TNBC. Moreover, our study showed that miR-3613-3p might be used as a predictive biomarker for the response of TNBC to Palbociclib.

Rescue experiments demonstrated that effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Up-regulation of miR-361-3p induced apoptosis and inhibited cell proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.

Our data indicate that miR-361-3p inhibits the Wnt/β-catenin protein signal by locking Wnt10A, which is an important factor in inhibiting the tumor in the pathogenesis of lymphoma. The miR-361-3p/Wnt10A axis may be a promising target for the treatment of lymphoma.

In addition, we also found that phosphorylation of AKT1 and MAPK3/1 co-transactivates RELA, thus constituting a RELA/JUN/miR-3613-5p/NR5A2/AKT1/MAPK3/1 positive feedback loop, leading to persistent NF-κB activation. Our findings also revealed that miR-3613-5p plays an oncogenic role in LUAD by promoting cell proliferation and acting as a key regulator of the positive feedback loop underlying the link between the NF-κB/RELA and AKT/MAPK pathways.

Two regulatory axes of BLACAT1-EZH2-MAPK and BLACAT1-HDAC1-STAT3 were identified to be associated with the progression of prostate cancer. Both chidamide and 5-azacytidine represent promising therapeutic options in prostate cancer treatment.

Preclinical studies using an in vivo mouse model with orthotopically xenografted CWR22Rv1 cells demonstrated that combining the Enz with the small molecule miR-361-3p would result in better suppression of the Enz-resistant PCa tumor progression. Together, these preclinical studies demonstrate that miR-361-3p can function via suppressing the expression of ARv7 and MKNK2 to maximally increase the Enz sensitivity, and targeting these newly identified Enz/miR-361-3p/ARv7 and/or Enz/miR-361-3p/MKNK2 signals with small molecules may help in the development of novel therapies to better suppress the CRPC in patients that already have developed the Enz resistance.