As an oncolytic virus, Newcastle disease virus (NDV) can specifically kill
tumor cells and has been tested as an attractive oncolytic agent for
cancer virotherapy.
Virus infection can trigger the changes of the cellular
microRNA (
miRNA) expression profile, which can greatly influence viral replication and pathogenesis. However, the interplay between NDV replication and cellular
miRNA expression in
tumor cells is still largely unknown. In the present study, we compared the profiles of cellular
miRNAs in uninfected and NDV-infected HeLa cells by small
RNA deep sequencing. Here we report that NDV
infection in HeLa cells significantly changed the levels of 40
miRNAs at 6 h post-
infection (hpi) and 62
miRNAs at 12 hpi. Among 23 highly differentially expressed
miRNAs, NDV
infection greatly promoted the levels of 3
miRNAs and suppressed the levels of 20
miRNAs at both time points. These 23
miRNAs are predicted to target various genes involved in virus replication and
antiviral immunity such as ErbB, Jak-STAT,
NF-kB and RIG-I-like receptor. Verification of deep sequencing results by quantitative RT-PCR showed that 9 out of 10 randomly selected
miRNAs chosen from this 23-miRNA pool were consistent with deep sequencing data, including 6 down-regulated and 3 up-regulated. Further functional research revealed that
hsa-miR-4521, a constituent in this 23-miRNA pool, inhibited NDV replication in HeLa cells. Moreover, dual-
luciferase and gene expression array uncovered that the member A of family with sequence similarity 129 (FAM129A) was directly targeted by
hsa-miR-4521 and positively regulated NDV replication in HeLa cells, indicating that
hsa-miR-4521 may regulate NDV replication via interaction with FAM129A. To our knowledge, this is the first report of the dynamic cellular
miRNA expression profile in
tumor cells after NDV
infection and may provide a valuable basis for further investigation on the roles of
miRNAs in NDV-mediated oncolysis.