Expression of noncoding vault RNA in human malignant cells and its importance in mitoxantrone resistance.
Several noncoding RNAs do vital cellular functions, including gene regulation and cell differentiation. Previously, we reported that vault RNA (vRNA) has the ability to recognize chemotherapeutic compounds, such as mitoxantrone, based on biophysical and biochemical analyses. In the present study, we show that human glioblastoma-, leukemia-, and osteocarcinoma-derived cell lines overexpress vRNA and exhibit higher resistance toward mitoxantrone. Interestingly, when vRNA expression was suppressed by RNA interference in these cells, the resistance progressively decreased. In agreement with these findings, overexpression of vRNA-1 caused resistance to mitoxantrone. These results suggest a role of vRNA in mitoxantrone resistance in malignant cells and justify further studies on the importance and application of noncoding RNAs in cancer chemotherapeutics.
Gopinath
Subash C B
SC
RNA Processing Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba City 305-8566, Ibaraki, Japan.
Wadhwa
Renu
R
Kumar
Penmetcha K R
PK
D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics; D008942:Mitoxantrone / Q000494:pharmacology*; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D020394:Vault Ribonucleoprotein Particles; D008942:Mitoxantrone