<p>Long Non-Coding RNA HOTAIR Modulates KLF12 to Regulate Gastric Cancer Progression via PI3K/ATK Signaling Pathway by Sponging miR-618</p>

Abstract

PurposeLong 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.MethodsThe 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.ResultsThe 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.ConclusionThese data unraveled that HOTAIR promoted GC progression through PI3K/ATK signaling pathway via miR-618/KLF12 axis.

Depletion of Circular RNA circ_CORO1C Suppresses Gastric Cancer Development by Modulating miR-138-5p/KLF12 Axis

“… 32 , 33 Furthermore, KLF12 was upregulated in GC, which could participate in lncRNA TTN-AS1 or HOTAIR-mediated GC progression. 34 , 35 Here, we also revealed the upregulation of KLF12 in GC. Functionally, overexpressed KLF12 attenuated the suppressive effect on GC cell proliferation and metastasis mediated by miR-138-5p.…”

Long Non-coding RNAs in Gammaherpesvirus Infections: Their Roles in Tumorigenic Mechanisms

“…HOTAIR can also affect GC cell cycle distribution by regulating P21 and P53 proteins ( Xu et al, 2019 ). HOTAIR could act as a ceRNA to repress miR-618 and subsequently increase KLF12 expression, inhibiting GC progression ( Xun et al, 2019 ). By interacting with miR-34a, HOTAIR may also be involved in the PI3K/Akt and Wnt/β-catenin signaling pathways ( Cheng et al, 2018 ).…”

Roles of the HOX Proteins in Cancer Invasion and Metastasis

“…Moreover, HOTAIR can act as a molecular sponge of miR-204, leading to an increase in HOXC8, promoting proliferation, migration and invasion in oesophageal cancer cells [128], whereas in cholangiocarcinoma, this process occurs through the modulation of miR-204-5p's interaction with HMGB1 [129]. Notwithstanding, HOTAIR promotes GC cell growth and metastasis by interfering in the miR-217/GPC5 [130], miR-1277-5p/COL5A1 [131], and miR-618/KLF12 axis, being that the last one induces metastasis by promoting the PI3K/ATK signalling pathway [132]. Recent findings have also related HOTAIR interference to Trastuzumab resistance in GC, through the sponging of miR-3030 and consequent upregulation of ERBB4 [133], which is responsible for activating the PI3K/ATK signalling pathway [134].…”