miR-26a induced the suppression of tumor growth of cholangiocarcinoma via KRT19 approach.
OBJECTIVE
KRT19 was identified as one of the key biomarkers for distinguishing cholangiocarcinoma (CCA) and hepatocellular carcinoma. The detailed role of miRNAs involved in the oncogenic incident of KRT19 was poor investigated.


RESULTS
Based on prediction and validation, miR-26a was inversely correlated with KRT19 in patients' tissues samples and biopsies. Ectopic expression of miR-26a dramatically suppressed cell proliferation and tumor growth in vitro and in vivo. Knock-down miR-26a could induce an increasing population of SP cells by promoting KRT19 expression. The KRT19 was also suppressed via directly binding at 3'UTR region by miR-26a.


METHODS
Bioinformatics prediction was first applied to screening the potential miRNA involved. RT-PCR, Immunohistochemistry and Western blot were used to examine the expression of miRNAs and candidate genes in 65 pairs of cholangiocarcinoma. The loss-and gain-function assay was employed to detect the role of certain miRNA in vitro and vivo. Side-population (SP) cells were detected and sorted by flow cytometry.


CONCLUSIONS
Aberrant decreased miR-26a could promote cell proliferation by regulating KRT19 which play important roles in the pathogenesis of CCA.
Department of Endocrinology, People's Hospital of Gaochun, Gaochun, Nanjing, 211300, Jiangsu Province, China.
Ping
P
Wang
Department of General Surgery, People's Hospital of Gaochun, Gaochun, Nanjing, 211300, Jiangsu Province, China.
Long
L
Lv
D020413:3' Untranslated Regions; D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053539:Keratin-19 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D034622:RNA Interference; D058985:Side-Population Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
D020413:3' Untranslated Regions; D053539:Keratin-19; D035683:MicroRNAs; C528163:MIRN26 microRNA, human
KRT19; cholangiocarcinoma; miRNA; proliferation; stem cell