MicroRNA-520c-3p Modulates Doxorubicin-Chemosensitivity in HepG2 Cells

Abstract

Background: Doxorubicin (DOX) is the most common drugs used in cancer therapy, including Hepatocellular Carcinoma (HCC). Drug resistance, is one of chemotherapy’s significant problems. Emerging studies have shown that microRNAs (miRNAs) could participate in regulating this mechanism. Nevertheless, the impact of miRNAs on HCC chemoresistance is still enigmatic. Objective: Investigating the role of miR-520c-3p in enhancement of anti-tumor effect of DOX against HepG2 cells. Methods: Expression profile for liver related miRNAs (384 miRNAs) has been analyzed on HepG2 cells treated with DOX using qRT-PCR. miR-520c-3p, the most deregulated miRNA, was selected for combination treatment with DOX. Expression level for LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53 was evaluated in miR-520c-3p transfected cells. Cell viability, colony formation, wound healing as well as apoptosis assays have been demonstrated. Furthermore, Mcl-1 protein level was measured using western blot technique. Results: The present data indicated that miR-520c-3p overexpression could render HepG2 cells chemo-sensitive to DOX through enhancing its suppressive effects on proliferation, migration, and induction of apoptosis. The suppressive effect of miR-520c-3p involved altering the expression levels of some key regulators of cell cycle, proliferation, migration and apoptosis including LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53. Interestingly, Mcl-1 was found to be one of the potential targets of miR-520c-3p, and its protein expression level was down-regulated upon miR-520c-3p overexpression. Conclusion: Our data referred to the tumor suppressor function of miR-520c-3p that could modulate chemosensitivity of HepG2 cells toward DOX treatment, providing a promising therapeutic strategy in HCC.

circKCNN2 suppresses the recurrence of hepatocellular carcinoma at least partially via regulating miR‐520c‐3p/methyl‐DNA‐binding domain protein 2 axis

“…miR‐520c‐3p was an important target of circKCNN2 and reversed the effects of circKCNN2 on HCC cells. Interestingly, miR‐520c‐3p was reported to enhance the chemo‐sensitivity of HepG2 cells to doxorubicin treatment 30 . This may be due to the fact that miR‐520c‐3p increases the proportion of cells at the S stage (Figure 7).…”

Novel Bis(2‐cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies

“…The potential of compounds 7 e and 7 f to trigger cell death in cancer cells was assessed using a flow cytometry assay in HCT116 cells utilizing 7-amino-actinomycin D (7-AAD) and protein Annexin-V. [56,57] In the early phases of apoptosis, phosphotidylserine (PS), which was previously inside the cell membrane, is translocated to the outside and forms a complex with annexin V. [58] The number of apoptotic cells is therefore strongly correlated with annexin V fluorescence, whereas 7AAD staining identifies necrotic cells. Cells stained with Annexin V-FTIC and 7AAD are discriminated as necrotic cells (Q1, annexin-V À /7AAD + ), late apoptotic cells (Q2, annexin-V + /7AAD + ), early apoptotic cells (Q3, annexin-V + /7AAD À ) and viable cells (Q4, annexin-V À /7AAD À ).…”

MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy

“…Additionally, they contribute to the transcription, post-transcriptional modifications, and signal transduction networking. MiRs are house-keeping molecules belonging to the small nucleolar RNAs (SnoRNAs) family [ 52 , 53 , 54 ]. In this section, we first provide an introduction about miRs and their biosynthesis, followed by a highlight of their potential roles in cancer.…”