ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies with high invasive and metastatic capability. Although significant advances have been made in the treatment of HCC, the overall survival rate of patients is still low. It is essential to explore accurate biomarkers for early diagnosis and prognosis along with therapeutic procedures to increase the survival rate of these patients. Anticancer therapies can contribute to induce apoptosis for the elimination of cancerous cells. However, dysregulated apoptosis and proliferation signaling pathways lead to treatment resistance, a significant challenge in improving efficient therapies. MiRNAs, short non-coding RNAs, play crucial roles in the progression of HCC, which regulate gene expression through post-transcriptional inhibition and targeting mRNA degradation in cancers. Dysregulated expression of multiple miRNAs is associated with numerous biological processes, including cell proliferation, apoptosis, invasion and metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and drug resistance in HCC. This review summarizes the role and potential efficacy of miRNAs in promoting and inhibiting cell proliferation and apoptosis in HCC, as well as the role of miRNAs in therapy resistance in HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , MicroRNAs/genetics , MicroRNAs/metabolism , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Signal Transduction/genetics , Epithelial-Mesenchymal Transition/genetics , Apoptosis/genetics , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , Cell Line, TumorABSTRACT
BACKGROUND: Gemini Curcumin (Gemini-Cur) is the latest nanoformulation of curcumin with a significant apoptotic effect on cancer cell lines. OBJECTIVE: This in vitro study aims to evaluate the apoptotic effects of Gemini-Cur toward MDA-MB-468 breast cancer cell lines and further the related mechanism of apoptosis. METHODS: The cytotoxicity of Gemini-Cur toward MDA-MB-468 cell lines was tested using MTT assay. Furthermore, the expression ratio of Bax/Bcl-2 was evaluated by qRT-PCR. Consequently, the protein expression of Bax/Bcl-2, survivin, and caspase-3 was measured using western blotting. RESULTS: Having treated MDA-MB-468 cell lines with Gemini-Cur, the IC50 values were found to be 44.44 and 31.63 µM at 24 and 48 h, respectively. Our findings showed that Gemini-Cur significantly suppresses cancer cell proliferation in a time- and dose-dependent manner. Furthermore, the data revealed that curcumin nanoformulation induces apoptosis in MDA-MB-468 cells through modulation of the expression of Bax, Bcl-2, Survivin, and Caspase-3. CONCLUSION: The data of the current study propose that Gemini-Cur can be considered a promising candidate against triple-negative breast cancer.