RESUMO
As a family of short noncoding RNAs, MicroRNAs have been identified as possible biomarkers for cancer discovery and assist in therapy control due to their epigenetic involvement in gene expression and other cellular biological processes. In the present review, the evidence for reaching the clinical effect and the molecular mechanism of miR-942 in various kinds of cancer is amassed. Dysregulation of miR-942 amounts in different kinds of malignancies, as bladder cancer, esophageal squamous cell carcinoma, breast cancer, cervical cancer, gastric cancer, colorectal cancer, Kaposi's sarcoma, melanoma, Hepatocellular carcinoma, nonsmall-cell lung cancer, oral squamous cell carcinoma, osteosarcoma, ovarian cancer, pancreatic ductal adenocarcinoma, renal cell carcinoma, and prostate cancer has stated a considerable increase or decrease in its level indicating its function as oncogene or tumor suppressor. MiR-942 is included in cell proliferation, migration, and invasion through cell cycle pathways, including pathways of transforming growth factor-beta signaling pathways, Wnt pathway, JAK/STAT pathway, PI3K/AKT pathway, apoptosis pathway, hippo signaling pathway, lectin pathway, interferon-gamma signaling, signaling by G-protein coupled receptor, developmental genes, nuclear factor-kappa B pathway, Mesodermal commitment pathway, and T-cell receptor signaling in cancer. An important biomarker, MiR-942 is a potential candidate for prediction in several cancers. The present investigation introduced miR-942 as a prognostic marker for early discovery of tumor progression, metastasis, and development.
RESUMO
Chemotherapy drugs are still one of the first treatment options used in many cancers; however, problems such as cytotoxic side effects on normal cells after systemic administration and resistance to treatment have reduced the use of chemotherapeutics day by day. Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer.