Title:Long Non-coding RNA SNHG16 Facilitates Esophageal Cancer Cell
Proliferation and Self-renewal through the microRNA-802/PTCH1
Axis
Volume: 29
Issue: 39
Author(s): Luquan Zhang, Hao Liang, Jinfeng Zhang, Yingnan Yang, Xiaodong Ling and Hao Jiang*
Affiliation:
- Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang
150000, P.R. China
Keywords:
SNHG16, esophageal cancer, microRNA-802, PTCH1, self-renewal, proliferation, Hedgehog pathway.
Abstract:
Objective: This research sought to explore the effect and mechanism of long
non-coding RNA SNHG16 on esophageal cancer (EC) cell proliferation and self-renewal.
Methods: SNHG16 expression was measured in EC9706 and KYSE150 cells. EC9706
and KYSE150 cells were transfected with Lenti-SNHG16, sh-SNHG16, Lenti-protein
patched homolog 1 (PTCH1), miR-802 mimic, or miR-802 inhibitor. Flow cytometry
was used to sort cancer stem cells (CSCs) in EC9706 and KYSE150 cells. Cell proliferation
in EC cells was measured, in addition to colony and tumorsphere numbers. The possible
interactions among SNHG16, PTCH1, and miR-802 were identified by dual luciferase
reporter and RNA pull-down assays. The expression of the genes in the Hedgehog
pathway was detected. Nude mice were injected with SNHG16-silenced EC9706
cells to observe the tumorigenicity of EC9706 cells.
Results: Upregulated SNHG16 expression was found in CSCs, whose expression was decreased
during the differentiation of CSCs. SNHG16 or PTCH1 overexpression or
miR-802 inhibition promoted the proliferation, colony formation, and tumorsphere formation
of EC9706 and KYSE150 cells as well as SOX2, OCT4, Bmi-1, and PTCH1 expression.
Consistently, SNHG16 knockdown or miR-802 overexpression inhibited EC progression.
Moreover, SNHG16 and PTCH1 were competitively bound to miR-802, and
SNHG16 orchestrated the miR-802/PTCH1 axis to activate the Hedgehog pathway. SNHG16
silencing repressed the tumorigenicity of EC9706 in nude mice.
Conclusion: Conclusively, SNHG16 acts as a sponge of miR-802 to upregulate PTCH1
and activate the Hedgehog pathway, thus promoting EC cell proliferation and selfrenewal.