Background: LncRNA is an important regulatory factor in the human genome. We aim to explore the roles of LncFALEC and miR-20a-5p/SHOC2 axis on the proliferation, migration, and Fluorouracil (5-FU) resistance of cholangiocarcinoma (CCA).

Methods: In this study, the expression of FALEC and miR-20a-5p in CCA tissues and cell lines (HuCCT1, QBC939, and Huh-28) was detected by RT-qPCR. The FALEC in 5-FU-resistant CCA cell lines (QBC939-R, Huh-28-R) was knocked down to evaluate its effects on cell proliferation, migration, invasion, and drug resistance.

Results: Our analysis showed that compared with the adjacent non-tumor tissues, FALEC was significantly higher in the CCA tissues and even higher in the samples from 5-FU-resistant patients. Knockdown FALEC increased the sensitivity of 5-FU and decreased migration and invasion of CCA cells. Dual luciferase reporter confirmed that FALEC sponges miR-20a-5p and down-regulated its expression. Moreover, SHOC2 leucine-rich repeat scaffold protein (SHOC2) was the target gene of miR-20a-5p. We found overexpression of FALEC (FALEC-OE) increased resistance of CCA cells to 5-FU significantly, which might contribute to increased SHOC2 expression and activation of the ERK1/2 signaling pathway.

Conclusions: In summary, our study revealed that down-regulation of FALEC could inhibit the proliferation, migration, and invasion of CCA cells in vitro by regulating the miR-20a-5p/SHOC2 axis and participating in 5-FU resistance by mediating the ERK1/2 signaling pathway.