Knockdown of long non-coding RNA plasmacytoma variant translocation 1 inhibits cell proliferation while promotes cell apoptosis via regulating miR-486-mediated CDK4 and BCAS2 in multiple myeloma.

AIMS: This study aimed to investigate the effect of long non-coding RNA-plasmacytoma variant translocation 1 (lnc-Pvt1) knockdown on regulating cell proliferation and apoptosis, and to explore its molecular mechanism in multiple myeloma (MM). METHODS: Lnc-Pvt1 expression was detected in MM cell lines (NCI-H929, U-266, LP-1 and RPMI-8226 cell lines) and human normal plasma cells. In U-266 cells and LP-1 cells, control shRNA and lnc-Pvt1 shRNA plasmids were transferred. Rescue experiments were further performed by transfection of lnc-Pvt1 shRNA alone and lnc-Pvt1 shRNA and miR-486 shRNA plasmids. Cells proliferation, apoptosis, RNA expression, and protein expression were determined by cell counting kit-8, annexin V-FITC-propidium iodide, quantitative polymerase chain reaction, and Western blot assays, respectively. RESULTS: Lnc-Pvt1 expression was increased in MM cell lines (NCI-H929, U-266 and LP-1 cell lines) compared with human normal plasma cells. In U-266 cells, lnc-Pvt1 shRNA suppressed cell proliferation while enhanced cell apoptosis compared with control shRNA. Also, lnc-Pvt1 shRNA increased miR-486 expression compared with control shRNA. Further rescue experiment revealed that miR-486 shRNA did not change lnc-Pvt1 level, but increased CDK4 and BCAS2 expressions in lnc-Pvt1 knockdown-treated cells. In addition, miR-486 shRNA promoted cell proliferation while inhibited cell apoptosis in lnc-Pvt1 knockdown-treated cells. These results were further validated in LP-1 cells. CONCLUSIONS: Lnc-Pvt1 knockdown inhibits cell proliferation and induces cell apoptosis through potentially regulating miR-486-mediated CDK4 and BCAS2 in MM.

The diagnostic value of human epididymis protein 4 as a novel biomarker in patients with renal dysfunction.

PURPOSE: In this study, we investigated the diagnostic value of human epididymis protein 4 (HE4) in acute and chronic renal dysfunction and analyzed the correlation between HE4 levels and the results of routine renal function tests. We aimed to provide evidence to establish HE4 as a novel biomarker of renal injury and its appropriate application as a marker of ovarian cancer. METHODS: We collected 259 serum samples from hospitalized patients with different causes of renal damage. HE4 serum levels were detected by chemiluminescence and the levels of serum creatinine, urea, and cystatin C were tested by conventional clinical chemical methods. RESULTS: The levels of HE4 were highest in the acute kidney injury groups and chronic kidney disease groups, although other groups were also significantly higher than the control group. HE4 and creatinine, urea, and cystatin C had a positive linear correlation. In contrast, HE4 and estimated glomerular filtration rate (eGFR) had a negative linear correlation, with a correlation coefficient of - 0.674 (P < 0.01). Area under the receiver-operating characteristic curve analysis showed that HE4 has higher diagnostic value compared with creatinine, urea, and cystatin C in both acute and chronic renal injury patients; however, HE4 and creatinine have a similar diagnostic value. Notably, HE4 concentration gradually increased with a decline of glomerular filtration rate, with significant differences evident between different eGFR stages. CONCLUSION: HE4 is a potential biomarker of kidney injury in acute and chronic renal dysfunction. Importantly, clinicians should be aware of this when using HE4 to diagnose ovarian cancer.