Roles of Long Noncoding RNAs in Recurrence and Metastasis of Radiotherapy-Resistant Cancer Stem Cells

Abstract

Radiotherapy is a well-established therapeutic regimen applied to treat at least half of all cancer patients worldwide. Radioresistance of cancers or failure to treat certain tumor types with radiation is associated with enhanced local invasion, metastasis and poor prognosis. Elucidation of the biological characteristics underlying radioresistance is therefore critical to ensure the development of effective strategies to resolve this issue, which remains an urgent medical problem. Cancer stem cells (CSCs) comprise a small population of tumor cells that constitute the origin of most cancer cell types. CSCs are virtually resistant to radiotherapy, and consequently contribute to recurrence and disease progression. Metastasis is an increasing problem in resistance to cancer radiotherapy and closely associated with the morbidity and mortality rates of several cancer types. Accumulating evidence has demonstrated that radiation induces epithelial–mesenchymal transition (EMT) accompanied by increased cancer recurrence, metastasis and CSC generation. CSCs are believed to serve as the basis of metastasis. Previous studies indicate that CSCs contribute to the generation of metastasis, either in a direct or indirect manner. Moreover, the heterogeneity of CSCs may be responsible for organ specificity and considerable complexity of metastases. Long noncoding RNAs (lncRNAs) are a class of noncoding molecules over 200 nucleotides in length involved in the initiation and progression of several cancer types. Recently, lncRNAs have attracted considerable attention as novel critical regulators of cancer progression and metastasis. In the current review, we have discussed lncRNA-mediated regulation of CSCs following radiotherapy, their association with tumor metastasis and significance in radioresistance of cancer.