Hsa_circ_0011290 regulates proliferation, apoptosis and glycolytic phenotype in papillary thyroid cancer via miR-1252/ FSTL1 signal pathway

Abstract

Objective: Despite of previous report regarding the aberrant overexpression of hsa_circ_0011290 in thyroid cancer, the regulatory mechanism and mechanistic involvements of which were still elusive currently in papillary thyroid cancer (PTC). Here we set out to characterize expression status and functional contributions of hsa_circ_0011290 in this disease especially through mode-of-action of sponging RNA.

Methods: Relative expression of hsa_circ_0011290, microRNA (miR)-1252 and FSTL1 was quantified by real-time polymerase chain reaction. Glucose metabolism was determined by examination of glucose uptake, lactate production and ATP contents. The regulatory effects of miR-1252 on both hsa_circ_0011290 and Follistatin Like 1 (FSTL1) were interrogated by luciferase reporter assay. Direct binding between miR-1252 with hsa_circ_0011290 and FSTL1 transcripts were analyzed by RNA pulldown assay. Protein levels of FSTL1 was examined by Western blots.

Results: Aberrant over-expression of hsa_circ_0011290 was associated with advanced stage and unfavorable prognosis of PTC. Knockdown of hsa_circ_0011290 greatly inhibited cell viability, proliferation and stimulated cell apoptosis in PTC cells. Meanwhile, glucose metabolism was significantly switched with decreased glucose uptake and lactate production, and increased ATP contents. We identified miR-1252 as target miR of hsa_circ_0011290, and miR-1252 evidently inhibited expressions of both luciferase reporter and endogenous hsa_circ_0011290, and miR-1252 was negatively regulated by hsa_circ_0011290 vice versa. We further suggested that FSTL1 as direct target of miR-1252, and provided direct evidences in support of binding between miR-1252 with both hsa_circ_0011290 and FSTL1. Through sponging miR-1252, hsa_circ_0011290 was capable of positively modulate FSTL1 expression. Notably, inhibition of miR-1252 completely reversed phenotypic effects of hsa_circ_0011290 knockdown including cell viability, proliferation, apoptosis and glucose metabolisms.

Conclusion: Our study uncovered the oncogenic contributions of hsa_circ_0011290-miR-1252-FSTL1 in PTCs.

Keywords: FSTL1; Thyroid cancer; hsa_circ_0011290; miR-1252.