LncRNA PMS2L2 Is Downregulated in Sepsis-Induced Acute Kidney Injury and Inhibits LPS-Induced Apoptosis of Podocytes.

INTRODUCTION: Long noncoding RNA PMS2L2 can inhibit inflammation induced by LPS, while LPS plays an important role in sepsis, indicating the possible involvement of PMS2L2 in sepsis. METHODS: Expressions of miR-21 and PMS2L2 in patients with acute kidney injury (AKI), sepsis patients without induced AKI, and healthy controls were determined by performing RT-qPCR. Overexpression assay was performed to explore the crosstalk between miR-21 and PMS2L2. Methylation-specific PCR (MSP) was performed to explore the role of PMS2L2 in regulating the methylation of miR-21 gene. The role of miR-21 and PMS2L2 in the apoptosis of CIHP-1 cells induced by LPS was assessed by cell apoptosis assay. RESULTS: PMS2L2 was downregulated in AKI patients induced by sepsis compared to sepsis patients without AKI and healthy controls. MiR-21 was also downregulated in AKI induced by sepsis and positively correlated with PMS2L2. In addition, in cells of human podocyte cell line (CIHP-1), overexpression of PMS2L2 promoted the expression of miR-21, while miR-21 did not affect the expression of PMS2L2. MSP analysis showed that overexpression of PMS2L2 decreased methylation of miR-21. LPS treatment downregulated PMS2L2 and miR-21 in a time-dependent manner. PMS2L2 and miR-21 decreased the apoptosis of CIHP-1 cells induced by LPS, and co-overexpression of PMS2L2 and miR-21 showed stronger inhibitory effect. CONCLUSION: PMS2L2 is downregulated in AKI induced by sepsis and inhibits LPS-induced apoptosis of podocytes.

Long Noncoding RNA PMS2L2 Downregulates miR-24 through Methylation to Suppress Cell Apoptosis in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colon. It has been reported that PMS2L2 plays protective roles in inflammatory injury. This study aimed to investigate the role of the long noncoding RNA PMS2L2 in UC. METHODS: Sixty-two patients with UC as well as 62 age- and gender-matched healthy controls were enrolled. Expressions of PMS2L2 and miR-24 in plasma from UC patients and healthy controls were determined by RT-qPCR. The interaction between PMS2L2 and miR-24 was predicted by bioinformatics and confirmed by RNA immunoprecipitation and RNA pull-down. The role of PMS2L2 in the regulation of miR-24 gene methylation was analyzed by methylation-specific PCR. The effects of PMS2L2 and miR-24 on the expressions of apoptosis-related proteins were detected by Western blots. RESULTS: PMS2L2 was downregulated in the plasma of UC patients compared to that in age- and gender-matched healthy control. In human colonic epithelial cells (HCnEpCs), PMS2L2 overexpression inhibited miR-24 expression via promoting the methylation of miR-24 gene. In contrast, miR-24 overexpression failed to affect PMS2L2. In the detection of cell apoptosis, PMS2L2 overexpression could promote the expression of Bcl-2 and inhibit Bax, cleaved-caspase-3, and cleaved-caspase-9 expressions stimulated by LPS. Flow cytometer revealed that PMS2L2 elevation suppressed the apoptosis of HCnEpCs induced by LPS, but miR-24 aggravated the apoptosis. PMS2L2 overexpression rescued the detrimental effect of miR-24 on cell apoptosis. CONCLUSION: PMS2L2 may downregulate miR-24 via methylation to suppress cell apoptosis in UC.

CXCL16 protects against oxygen and glucose deprivation-induced injury in human microvascular endothelial cells-1: Potential role in ischemic stroke.

AIM: To explore the protective effect of chemokine ligand 16 (CXCL16) against cell damage induced by oxygen-glucose deprivation (OGD) in human microvascular endothelial cells-1 (HMEC-1) and its possible mechanism. METHODS: Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to determine cell viability and apoptosis of HMEC-1, respectively. qRT-PCR analysis was applied to display the expression of CXCL16 and miR-424. Western blot analysis was used to detect the expression of apoptosis-related proteins, CXCL16, cAMP/PKA/CREB, and PI3K-AKT-GSK3ß pathway-related proteins. RESULTS: OGD significantly inhibited cell viability and promoted apoptosis. CXCL16 overexpression decreased the proliferation inhibition and apoptosis of HMEC-1 induced by OGD. Furthermore, we found that CXCL16 was a target of miR-424 and was downregulated by miR-424. The further study showed that overexpression of miR-424 significantly increased proliferation inhibition and apoptosis of HMEC-1 induced by OGD. In addition, we also found that miR-424 was downregulated by PMS2L2. In the subsequence experiment, overexpression of PMS2L2 significantly decreased the proliferation inhibition and apoptosis of HMEC-1 induced by OGD, which suggested that PMS2L2 decreased cell damage of HMEC-1 induced by OGD. Simultaneously, CXCL16 treatment markedly increased the phosphorylation of PKA/CREB and PI3K-AKT-GSK3ß and these signal pathways were blocked by signal inhibitors. CONCLUSION: Our study first demonstrates that oxygen-glucose deprivation (OGD)-induced human microvascular endothelial cells-1 (HMEC-1) cell injury was alleviated by CXCL16 targeted by miR-424 which further targeted by PMS2L2. This process might also be regulated by activating PKA/CREB and PI3K-AKT-GSK3ß pathways.

Long non-coding RNA PMS2L2 is down-regulated in osteoarthritis and inhibits chondrocyte proliferation by up-regulating miR-34a.

Long non-coding RNA (lncRNA) PMS2L2 has been reported to participate in endotoxin-induced inflammatory responses. As these types of responses can promote osteoarthritis (OA), it was of interest to ascertain if PMS2L2 may be involved in OA. To explore any potential participation of PMS2L2 in OA, synovial fluid was extracted from both OA patients and healthy controls (n = 62 each) and PMS2L2 expression of each sample determined by RT-qPCR. In addition, as miR-34a has a potential binding site on PMS2L2, hypothetical interactions between PMS2L2 and miR-34a in chondrocytes were analyzed by performing over-expression experiments. Furthermore, the role of PMS2L2 and miR-34a in the regulation of chondrocyte proliferation was analyzed using CCK-8 and BrdU assays. The results showed that PMS2L2 expression in OA patient synovial fluid was lower compared to that in control group fluid, and the extent of this reduction was related to disease stage. In in vitro studies, it was seen that endotoxin treatment of chondrocytes led to decreased PMS2L2 expression. It was found that PMS2L2 over-expression caused increased miR-34a expression in OA patient chondrocytes but not in cells from healthy controls. In contrast, miR-34a over-expression in either cell population did not affect PMS2L2 expression. Lastly, over-expression of both PMS2L2 and miR-34a led to inhibited chondrocyte proliferation. Of note, a combined over-expression of PMS2L2 and miR-34a resulted in stronger effects on proliferation compared to that from either single over-expression. Based on the findings that PMS2L2 is down-regulated during ongoing states of OA, and that changes in PMS2L2 expression can lead to increases in chondrocyte expression of miR-34a - resulting in inhibition of chondrocyte proliferation in OA. From these findings, one may conclude that finding means to regulate PMS2L2 could be a promising new target in the development of regimens for the treatment of OA.

Downregulation Of LncRNA PMS2L2 In Endometrial Adenocarcinoma Upon Carboplatin Treatment.

BACKGROUND: LncRNA PMS2L2 plays critical protective roles in chondrocytes during lipopolysaccharide-induced inflammation. Our preliminary deep sequencing revealed the altered expression of PMS2L2 in endometrial adenocarcinoma (EA) during chemotherapy. This observation triggered our interest to explore the functions of PMS2L2 in EA. METHODS: Levels of PMS2L2 in plasma were measured by qPCR. ROC curve analysis was used for diagnostic analysis. Cell viability was analyzed by cell viability assay. RESULTS: We showed that plasma PMS2L2 was downregulated in EA patients compared with healthy controls, and downregulation of PMS2L2 distinguished early-stage EA patients from healthy controls. During carboplatin-based chemotherapy, plasma levels of PMS2L2 were significantly downregulated in endometrial cancer patients. Overexpression of PMS2L2 led to decreased viability of EA cells, while PMS2L2 siRNA silencing led to increased viability of EA cells. CONCLUSION: LncRNA PMS2L2 in endometrial cancer was downregulated during carboplatin treatment and regulates chemosensitivity.

RETRACTED: LncRNA PMS2L2 protects ATDC5 chondrocytes against lipopolysaccharide-induced inflammatory injury by sponging miR-203.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Given the comments of Dr Elisabeth Bik regarding this article "… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.