The human genome contains thousands of long intergenic noncoding RNAs (lincRNAs). However, the functional roles of these transcripts and the mechanisms responsible for their deregulation in colorectal cancer (CRC) remain elusive. Researchers at Sun Yat-sen University found a novel lincRNA termed upregulated in CRC (UCC) was highly expressed in human CRC tissues and cell lines. UCC levels correlated with lymph node metastasis, Dukes’ stage, and patient outcomes. In SW480 and SW620 cells, knockdown of UCC inhibited proliferation, invasion, and cell cycle progression and induced apoptosis in vitro. Xenograft tumors grown from UCC-silenced SW620 cells had smaller mean volumes and formed more slowly than xenograft tumors grown from control cells. Inversely, overexpression of UCC in HCT116 promoted cell growth and invasion in vitro. Bioinformatics analysis, dual-luciferase reporter assays, and RNA immunoprecipitation assays showed that miR-143 can interact with UCC, and we found that UCC expression inversely correlates with miR-143 expression in CRC specimens. Moreover, mechanistic investigations showed that UCC may act as an endogenous sponge by competing for miR-143, thereby regulating the targets of this miRNA. These results suggest that UCC and miR-143 may be promising molecular targets for CRC therapy.
UCC knockdown inhibits CRC cell growth in vitro and in vivo
(a) UCC expression levels were suppressed by specific siRNAs in CRC cells. (b) Growth curves of SW620 and SW480 cells after transfection with si-UCC or si-NC were determined via MTS assays. (c) The anchorage-independent growth of SW620 and SW480 cells was assessed via colony formation assays. (d) Cell proliferation was evaluated using EdU incorporation assays. Proliferating cells were labeled with EdU. Scale bar: 200 μm. (e) Effects of UCC knockdown on tumor growth after 4 weeks in vivo (n=5 per group). Upper: negative control cells. Lower: representative images of tumors formed in nude mice subcutaneously injected with UCC-silenced SW620 cells. (f) Growth curves of xenograft tumors after subcutaneous injection of mice with UCC-silenced SW620 or negative control cells. The tumor volumes were measured every 5 days after inoculation. (n=5). (g) Immunohistochemical staining showed that UCC knockdown decreased the Ki-67 proliferation index. The data were represented as the mean±S.D. of three independent experiments in vitro or five independent experiments in vivo. *P<0.05, **P<0.01 by Student’s t-test