No abstract

We investigated the role of actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) lncRNA in promoting cholangiocarcinoma (CCA). qRT-PCR analysis of patient samples showed that AFAP1-AS1 expression was higher in CCA tumors than matched adjacent non-tumor tissue. AFAP1-AS1 levels were also higher in CCA cell lines (HuCCT1 and TFK-1) than a normal biliary epithelium cell line (HIBEpic). AFAP1-AS1 knockdown in CCA cell lines using shAFAP1-AS1 reduced cell proliferation and colony formation in CCK-8 and colony formation assays, respectively. Cell cycle analysis demonstrated that AFAP1-AS1 knockdown resulted in G0/G1 cell cycle arrest and inhibition of S-G2/M transition compared to the controls. CCA cells transfected with shAFAP1-AS1 also exhibited reduced metastasis and invasiveness in Transwell and wound healing assays. This was further confirmed in xenograft experiments with nude mice using CCA cells transfected with shAFAP1-AS1 or control shRNA. AFAP1-AS1 knockdown cells produced smaller tumors, demonstrating that AFAP1-AS1 promotes tumor growth in vivo. AFAP1-AS1 knockdown also increased expression of actin filament associated protein 1 (AFAP1) and reduced cell stress filament integrity, as determined from western blot and immunofluorescence assays, respectively. These findings indicate that AFAP1-AS1 exerts oncogenic effects in CCA. We postulate that AFAP1-AS1 is a potentially useful diagnostic and prognostic biomarker and therapeutic target for CCA.

Dysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.