Long Non-Coding RNA HOTAIR Modulates KLF12 to Regulate Gastric Cancer Progression Via PI3K/ATK Signaling Pathway by Sponging MiR-618

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Dec 11

PMID 31819516

Citations 13

Authors

Jin Xun

Chunfeng Wang

Jianning Yao

Bing Gao

Lianfeng Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: Long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) has been reported to dysregulate in many tumors. However, the mechanism of HOTAIR was rarely reported in GC.

Methods: The levels of HOTAIR, microRNA-618 (miR-618) and Krueppel-like factor 12 (KLF12) in GC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and apoptotic rate were assessed via cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The migrating and invading abilities were tested by Transwell assay. The protein levels of KLF12, p-PI3K, PI3K, p-ATK and ATK were measured by Western blot assay. These interactions between miR-618 and HOTAIR or KLF12 were predicted by DIANA tools, and then, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to validate these interactions. Besides, the xenograft tumor experiment was performed to further verify the roles of HOTAIR in GC.

Results: The levels of HOTAIR and KLF12 were significantly upregulated and the level of miR-618 was strikingly downregulated in GC tissues and cells. miR-618 was verified as a direct target of HOTAIR or KLF12. HOTAIR silencing blocked GC progression and PI3K/ATK signaling pathway by sponging miR-618 and also restrained xenograft tumor growth in vivo. miR-618 inhibited GC progression and PI3K/ATK signaling pathway by targeting KLF12. Mechanistically, HOTAIR modulated KLF12 expression by sponging miR-618 in GC cells.

Conclusion: These data unraveled that HOTAIR promoted GC progression through PI3K/ATK signaling pathway via miR-618/KLF12 axis.

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