LINC00294 induced by GRP78 promotes cervical cancer development by promoting cell cycle transition

Abstract

Cervical cancer is one of the most common gynecological malignancies, and it has become a crucial public health problem. In the present study, the expression profiles of cervical cancer and normal cervical tissues were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Subsequently, the dysregulated long non-coding RNAs (lncRNAs) in cervical cancer were identified using R software Differentially expressed lncRNAs in cervical cancer that were associated with glucose-regulated protein 78 (GRP78) were screened out and the results demonstrated that eight lncRNAs were strongly positively correlated with GRP78. In order to confirm the relationship between GRP78 and candidate lncRNAs, GRP78 small interfering RNA (siRNA) was transfected into HeLa cells. The target lncRNAs that were regulated by GRP78 were then identified by reverse transcription-quantitative PCR and it was revealed that LINC00294 was significantly downregulated following GRP78-knockdown. Subsequently, Gene Set Enrichment Analysis demonstrated that LINC00294 was mainly enriched in regulating the cell cycle and the Hedgehog pathway. Following transfection of HeLa and SiHa cells with LINC00294 siRNA, the cell cycle was arrested at the G0/G1 phase. Western blotting suggested that LINC00294-knockdown downregulated the expression of cell cycle-associated factors (cyclin D, cyclin E and cyclin Dependent kinase 4) and upregulated cell cycle inhibitory factors (p16 and p21). The Hedgehog pathway was inhibited following knockdown of LINC00294 in HeLa and SiHa cells. In summary, LINC00294 induced by GRP78 promoted the progression of cervical cancer by regulating the cell cycle via Hedgehog pathway.

Silencing LINC00294 Restores Mitochondrial Function and Inhibits Apoptosis of Glioma Cells under Hypoxia via the miR‐21‐5p/CASKIN1/cAMP Axis

“…Notably, the aberrant lncRNA expression is implicated in glioma initiation and progression, and consequently, lncRNAs can function as competent biomarkers for the diagnosis, prognosis, and target therapy of glioma [ 13 ]. Qiu et al have revealed that LINC00294 facilitates cervical cancer progression by regulation of the cell cycle via the Hedgehog pathway [ 14 ]. Notably, the NONCODE database indicated that LINC00294 is upregulated in the normal brain tissues, and GEPIA suggests that LINC00294 is notably downregulated in glioblastoma (GBM) tissues [ 15 ].…”

LPI-EnEDT: an ensemble framework with extra tree and decision tree classifiers for imbalanced lncRNA-protein interaction data classification

“…More importantly, NEFM, a tumor suppressor, was reported to be significantly reduced in cancerous conditions and boost in glioma cells through LINC00294 up-regulation [ 50 ]. LINC00294 induced by GRP78 may still promote the progression of cervical cancer [ 51 ]. In addition, Bak-IIIa may improve LPS-induced inflammatory damage in HUVECs through upregulating LINC00294 [ 52 ].…”

Overexpression of Eukaryotic translation initiation factor 3D induces stem cell-like properties and metastasis in cervix cancer by activating FAK through inhibiting degradation of GRP78

“…Importantly, GRP78 is one of the markers of cancer stem cells [ 15 ]. The high expression of GRP78 could promote the stem cell-like properties of cervix cancer [ 25 ]. Interestingly, we also noticed here that EIF3D could promote the stem cell-like properties of cervix cancer via GRP78.…”