Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide, accounting for approximately 90 % of primary liver cancer, characterized by high mortality, recurrence, metastasis and poor prognosis [1]
The mechanisms involved in HCC drug resistance are complex and include the increased expression of drug efflux transporters that recognize and pump out anticancer drugs out of tumor cells, redistribution of intracellular accumulation of agents, inactivation of apoptosis signaling pathways, enhanced DNA damage repair capacity, accelerated drug metabolism and activation of cancer stem cells (CSCs) [5–7]
We systematically summarize the literatures on miRNAs and long ncRNAs (lncRNAs) modulating HCC drug resistance as well as the underlying mechanisms, thereby providing insight into the role of ncRNAs as putative biomarkers and/or therapeutic targets of HCC in the future
Summary
Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide, accounting for approximately 90 % of primary liver cancer, characterized by high mortality, recurrence, metastasis and poor prognosis [1]. Exogenous expression of miR-519d has been found to increase resistance of HCC cells to adriamycin by targeting multiple tumor suppressor genes, including p21 and PTEN [77].
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