LINC01121 Inhibits Cell Apoptosis While Facilitating Proliferation, Migration, and Invasion Though Negative Regulation of the Camp/PKA Signaling Pathway via GLP1R

Abstract

Background/Aims: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. Methods: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. Results: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. Conclusion: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

<p>Long Intergenic Non-Coding RNA 01121 Promotes Breast Cancer Cell Proliferation, Migration, and Invasion via the <em>miR-150-5p</em>/HMGA2 Axis</p>

“…These results indicated that LINC01121 acts as an oncogene and is involved in the process of breast cancer proliferation, migration, and invasion. Qian et al 10 reported that LINC01121 is overexpressed and acts as an oncogene in pancreatic cancer tissues, which is similar to our results. One of the functions of lncRNAs is to act as miRNA sponges to regulate the expression of their miRNA targets.…”

“…LINC01121 has been reported to be aberrantly expressed and act as an oncogene in pancreatic cancer. 10 Huang et al 11 reported that pterostilbene could suppress proliferation and epithelial-to-mesenchymal transition and promote apoptosis in breast cancer cells. Further investigation showed that pterostilbene can decrease the expression of LINC01121, suggesting that LINC01121 may act as an oncogene in breast cancer.…”

Long Non-coding RNAs Contribute to the Inhibition of Proliferation and EMT by Pterostilbene in Human Breast Cancer

“…The results of the present study also demonstrated decreased expression of the lncRNAs LINC01121, PTTG3P and HOTAIR following pterostilbene treatment. In pancreatic cancer, LINC01121 is shown to inhibit cell apoptosis and promote cell proliferation, migration and invasion via interaction of GLP1R in the control of the Camp/PKA signaling pathway (37). In hepatocellular carcinoma, enforced expression of the lncRNA PTTG3P facilitates cell proliferation, invasion, migration, and metastasis via activation of the PI3K/Akt pathway (38).…”

LRRC75A antisense lncRNA1 knockout attenuates inflammatory responses of bovine mammary epithelial cells

“…Long noncoding RNAs (LncRNAs) are transcripts with length of at least 200 nucleotides featuring limited protein-coding capability and poorly conserved sequence among mammalian species, and they account for about 98% of transcripts in human genome [4]. LncRNA has been reported to be involved in various biological behaviors, such as the regulation of cell proliferation, apoptosis, autophagy and migration [5][6][7][8]. Some lncRNAs are reported to involve in the modulation of maintain normal tissue structure and permeability [9][10][11].…”