LOC646329 long non-coding RNA sponges miR-29b-1 and regulates TGF β signaling in colorectal cancer

AbstractNon-coding RNAs (ncRNAs) are reported to be regulators of signaling pathways that are involved in colorectal cancer (CRC) progression. Aiming at finding ncRNAs (miRNAs) that are differentially expressed in tumor versus normal colorectal tissue samples, online RNA-seq data were analyzed. Of between 18 candidate miRNAs,hsa-miR-29b-1 (miR-29b-1) represented the highest fold change of expression level.Hsa-miR-29b-1 is encoded from the third intron ofLOC646329 long ncRNA gene. Surprisingly, twomiR-29b sponging sites were predicted within exons ofLOC646329 gene. Then, dual luciferase assay supported the interaction ofmiR-29b-1 withLOC646329-variant D transcript. Also, a direct indication ofmiR-29b-1 with 3 ′UTR sequence ofSMAD3 gene was verified through dual luciferase assay and RT-qPCR analysis. Furthermore, a reverse pattern of expression was detected betweenmiR-29b-1 andLOC646329-variant D transcript in about 25 pairs of CRC tumor samples, detected by RTqPCR. Consistently, overexpression ofLOC646329-variant D transcript was followed by increasedSMAD3 andp21 genes expression level and downregulation of CyclinD1 genes in HCT116 cells, detected by RT-qPCR, and western analysis. Also, overexpression of it was followed by increased G1 cell population of HCT-116 cells. All of these data suggested a tumor suppressor effect forLOC646329-variant D in CRC tumor tissue samples, consistent to its reduced expression level at late stages of CRC progression. Data also indicated thatL...
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research