Promotion of cell autophagy and apoptosis in cervical cancer by inhibition of long noncoding RNA LINC00511 via transcription factor RXRA‐regulated PLD1

Abstract

An increasing number of studies have explored the relationship of long noncoding RNAs (lncRNAs) with cervical cancer, yet the role of LINC00511 in cervical cancer still remains elusive. The current dissertation was intended to explore the effect of LINC00511 on cervical cancer development by regulating phospholipase D1 (PLD1) expression through transcription factor retinoic X receptor alpha (RXRA). Differentially expressed lncRNA and messenger RNA related to cervical cancer were screened by microarray-based expression profiling. Cervical cancer and paracancerous tissues were harvested to determine the LINC00511 expression using reverse transcriptionquantitative polymerase chain reaction and western blot analysis. The relationship among LINC00511, PLD1 promoter activity, and RXRA were determined via RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Proliferation, autophagy, and apoptosis of cervical cancer cells were detected with a series of experiments. Tumor xenograft in nude mice was employed to determine the influence of LINC00511 and PLD1 on tumor formation and growth of cervical cancer in vivo. LINC00511 might influence the occurrence of cervical cancer by upregulating PLD1 expression via recruiting transcription factor RXRA. LINC00511 and PLD1 expressions were remarkably high in cervical cancer tissues and cells. LINC00511 combined with RXRA, and overexpression of LINC00511 in cervical cancer cells elevated PLD1 expression. Si-LINC00511, si-RXRA or si-PLD1 triggered repression of proliferation and promotion of autophagy and apoptosis of cervical cancer cells. In vivo experiment, si-LINC00511, or si-PLD1 inhibited the tumorigenic ability of nude mice. Collectively, this study suggests that LINC00511 acts as an oncogenic lncRNA in cervical cancer via the promotion of transcription factor RXRA-regulated PLD1.

<p>Long Non-Coding RNA LINC00511 Accelerates Proliferation and Invasion in Cervical Cancer Through Targeting miR-324-5p/DRAM1 Axis</p>

“…Shi et al reveal that LINC00511 regulates the expression of PLD1 via accumulation of transcription factor RXRA in the promoter region of the PLD1 in HeLa cells. 23 In the present study, we confirmed that LINC00511 was mostly expressed in the cytoplasm of cervical cancer cells, which may function as a ceRNA. LINC00511 is also reported to amass in cytoplasm in gastric cancer 29 and pancreatic adenocarcinoma cells.…”

“…16 Previous studies have revealed that LINC00511 is also up-regulated in cervical cancer and associated with poor prognosis, and serves as an oncogene gene in HPV-positive cervical cancer cells. 20,23 Herein, what we have in common with previous research was that LINC00511 was significantly up-regulated in cervical cancer and promoted tumor development. In addition, this study revealed, for the first time, the promoting effect of LINC00511 on HPV-negative cervical cancer cells.…”

“…22 Shi et al report that LINC00511 knockdown inhibits the proliferation and promotes apoptosis and autophagy of HeLa cells. 23 However, it is unclear whether LINC00511 performs similar functions in cervical cancer cells, particularly in HPV-negative cells, as it has not been studied.…”

Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation

“…RXRa is a member of the nuclear receptor (NR) superfamily, which functions in the regulation of transcription, and in controlling the development, homeostasis, and metabolism of organisms (53). RXRa is downregulated in cervical cancer and inhibits its progression (54). In this study, proteomics analysis and bioinformatics prediction showed that the ITCH promoter contains a DNA binding site for RXRa, and ITCH and RXRa were consistently upregulated.…”

LncRNA LINC00511 plays an oncogenic role in lung adenocarcinoma by regulating PKM2 expression via sponging miR‐625‐5p

“…In cervical cancer, inhibition of LINC00511 was found to promote cell apoptosis and autophagy via RXRA-regulated PLD1. 21 In hepatocellular carcinoma, overexpression of LINC00511 was correlated with poor prognosis, and promoted cell metastasis and proliferation by regulating of miR-424. 22 LINC00511 functioned as a competing endogenous RNA to regulate VEGFA via sponging miR-29b-3p in pancreatic ductal adenocarcinoma.…”