Modulating Levels of miR 204-5p Could Become a Therapeutic Approach for Melanoma


The microRNA member miR-204-5p inhibits apoptosis in melanoma cells treated with dacarbazine or when overexpressed.

MicroRNA (miR/miRNA) can regulate the efficacy of chemotherapy for melanoma by modulating apoptosis—or cell cycle arrest— in cancer cells, according to the results of a recent study published in Oncology Research. miR-204-5p is a member of the miRNA oncosuppressor family that was shown to reduce apoptosis in cancer cells treated with dacarbazine (DTIC-Dome; Bayer) or in cells that had an overexpression of miR-204-5p.

Credit: Christoph Burgstedt -

Credit: Christoph Burgstedt -

“miR-204-5p could affect cancer cell resistance to chemotherapeutic drugs mostly via modulating apoptosis,” the study authors wrote in the article. “Therefore, miR-204-5p could be involved in the apoptosis of melanoma cells triggered by DTIC or miR-204-5p overexpression.”

Chemotherapy is the standard of care for melanoma, but it is associated with high levels of drug resistance and low efficacy. While its mechanisms for evading treatment are not entirely known, previous literature suggests that miRNA expression may be associated with chemotherapy efficacy.

miRNAs are small, non-coding RNAs that regulate gene expression by acting as oncogenes and oncosuppressor genes in cancer cells. miR-204-5p is a particular type of miRNA oncosuppressor in cancer cells that may block the cancer cell cycle by keeping it in resting phase (G0), that way it does not produce more cancer cells.

“Among the miRNAs that regulate cell cycle and, therefore, cancer cell transition to the G0 phase of the cell cycle, miR-204-5р is considered as an oncosuppressor gene,” the study authors wrote when discussing previous research.

However, the gene has also been associated with cell metastasis and drug resistance to treatments, such as BRAF inhibitors.

The current study aimed to understand how dacarbazine (DTIC) alters the miR-204-5p cell cycle in melanoma cells. Investigators transfected DTIC-treated melanoma cells with either a specific analogue (mimic) for hsa-miR-204-5p, a corresponding negative control miRNA, or a corresponding positive control. Then the team determined the proportion of melanoma cells in G0 phase, identified miRNAs and mRNA gene expression levels, measured cell proliferation using the Ki-67 biomarker, then determined the proportion of melanoma cells that were apoptotic.

The results showed that melanoma cells treated with DTIC had a higher ratio of early apoptotic cells; however, when miR-204-5p became overexpressed in DTIC-treated cells, there was a smaller proportion of early apoptotic melanoma cells.

This ultimately means that “cell apoptosis can be both triggered and inhibited by miR-204-5p,” according to study authors.

Treatment was also found to increase the proportion of Ki-67 negative cells by 3%. The Ki-67 protein is a biomarker of increased cancer cell proliferation in patients with malignant tumors, and increased expression may be associated with worse survival outcomes; however, it was a small enough percentage to not be considered severe.

Investigators further discovered that the DTIC-treated cells that were introduced to the mimic miR-204-5p gene actually caused the overexpression of miR-204-5p, which may suggest that the introduction of tools that regulate this pathway can lead to increased efficacy of chemotherapy with less resistance.


Palkina A, Sergeeva E, Ruksha T. miR 204-5p inhibits apoptosis in dacarbazine-treated melanoma cells. Oncol Res. 2021; 29(6): 393–400. doi: 10.32604/or.2022.025816

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