Long non‑coding RNA LINC01006 exhibits oncogenic properties in cervical cancer by functioning as a molecular sponge for microRNA‑28‑5p and increasing PAK2 expression

Abstract

As previously reported, long intergenic non-protein-coding RNA 1006 (LINc01006) plays crucial roles in prostate, pancreatic and gastric cancers. However, whether it plays important roles in cervical cancer remains unclear. The present study thus aimed to determine the precise role of LINc01006 in cervical cancer and elucidate its regulatory mechanisms. The expression of LINc01006 in cervical cancer was examined by reverse transcription-quantitative polymerase chain reaction. Cell proliferation assay, flow cytometric analysis, Transwell migration and invasion assays, and tumor xenograft model experiments were performed to elucidate the roles of LINc01006 in cervical cancer. Bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation and rescue experiments were performed for mechanistic analyses. The expression of LINc01006 was found to be upregulated in cervical cancer and to be associated with a poor prognosis. The absence of LINc01006 inhibited the proliferation, migration and invasion of cervical cancer cells, whereas it promoted cell apoptosis in vitro. The downregulation of LINc01006 impeded tumor growth in vivo. LINc01006 was verified as an endogenous 'sponge' that competed for microRNA-28-5p (miR-28-5p), which resulted in the upregulation of the miR-28-5p target P21-activated kinase 2 (PAK2). Rescue experiments revealed that the suppression of miR-28-5p expression or the overexpression of PAK2 abrogated the effects of LINc01006 downregula-tion on malignant cellular functions in cervical cancer. On the whole, the present study demonstrates that LINc01006 exhibits tumor-promoting functions in cervical cancer via the regulation of the miR-28-5p/PAK2 axis. These findings may provide the basis for the identification of LINC01006-targeted clinical therapy.

LINC01006 and miR-3199 Serve as Novel Markers of Poor Prognosis in Colon Cancer and Regulate Cell Proliferation, Migration and Invasion

“… 29 LINC01006 is upregulated in cervical cancer and indicated a poor prognosis. 16 miR-3199 could serve as a mighty biomarker for recurrence prediction among patients with hepatocellular carcinoma 30 and contribute towards survival prediction of lung adenocarcinoma. 31 In this study, we detected LINC01006 and miR-3199 in colon cancer tissues and cells at an elevated and a reduced expression level, respectively, via RT-qPCR.…”

“…LncRNAs exert their functions by multiple mechanisms, in which functioning as decoys and scaffolds of miRNAs, so-called miRNA “sponges”, was the main way. 32 LINC01006 has been proved as miR-28-5p sponge in cervical cancer, 16 miR-129-2-3p sponge in lung Adenocarcinoma. 33 By using bioinformatics analysis and experimental verification, we found LINC01006 was a sponge of miR-3199 in colon cancer cells.…”

“… 14 , 15 LINC01006, one kind of long intergenic noncoding RNA (lincRNA), participates in much cellular physiology such as carcinogenesis, proliferation, and metastasis. 16–18 Not only LINC01006 could act as functional molecules and regulators for cellular physiology, but also biomarkers in the tumor. A study about biomarkers of gastric cancer suggested LINC01006 might serve as a potent and new prognostic predictor for gastric cancer.…”

LncRNA CDKN2B‑AS1 sponges miR‑28‑5p to regulate proliferation and inhibit apoptosis in colorectal cancer

“…It was identified that miR-28-5p directly targeted CDKN2B-AS1. The localization of miR-28-5p in the cytoplasm and its interaction with lncRNAs have been studied in numerous cancers including CRC (23,24). Moreover, the results revealed that the expression of miR-28-5p was negatively correlated with the expression of CDKN2B-AS1 in CRC tissues and cell lines.…”

MicroRNA-194-5p Attenuates Doxorubicin-Induced Cardiomyocyte Apoptosis and Endoplasmic Reticulum Stress by Targeting P21-Activated Kinase 2

“…P21-activated kinase 2 (PAK2), a Rac1/Cdc42 activated signaling effector, belongs to the PAK family of serine/threonine kinases (20). The antiapoptotic effect of PAK2 has been demonstrated in multiple cancer studies (21)(22)(23). Recently, PAK2 has been reported to exert cardioprotective role by improving ER function through the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1)-dependent pathway (24).…”