Identification of therapeutic miRNAs from the arsenic induced gene expression profile of hepatocellular carcinoma.

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with a rising worldwide burden due to a lack of efficient treatment techniques and diagnosis after it has metastasized. Therefore, small non-coding RNA (miRNAs) as protein translation inhibitors are gaining attention that degrades or suppress specific gene transcripts, making it a prime strategy for oncogenes or tumor suppression. Systematic research with miRNAs in combination with Arsenic, which has been employed as a drug to treat several diseases, including cancer, was focused on cellular responses through interacting with multiple biological targets. The differential gene expression of the DNA microarray dataset (GSE48441) revealed the association of sterol, cholesterol, and lipid metabolic processes. With the aid of the network pharmacology approach, hsa-mir-335-5p was uncovered to negatively regulate the important nodes driving the transport and utilization of essential compounds for the rapid growth and proliferation of cancer cells. The binding energies of the duplexes were validated by the minimal free energies of the mRNAs for hsa-mir-335-5p, indicating energetically desirable binding association. The molecular interactions between hsa-mir-335-5p, which interacts with the Argonaute protein in the RNA induced silencing complex, and the target-specific genes were also investigated, revealing its susceptibility to be employed in in vitro studies.