bims-lorfki 2021-11-21 papers

Issue of 2021‒11‒21
three papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Bioengineered. 2021 Nov 16.

LncRNA KCNQ1OT1 (potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1) aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 (mitogen-activated protein kinase 1) axis in sepsis.

Haixia Wang, Hongbin Mou, Xiaolan Xu, Changhua Liu, Gang Zhou, Bo Gao.

Acute kidney injury (AKI), a common complication of sepsis, is characterized by a rapid loss of renal excretory function. A variety of etiologies and pathophysiological processes may contribute to AKI. Previously, mitogen-activated protein kinase 1 (MAPK1) was reported to regulate cellular processes in various sepsis-associated diseases. The current study aimed to further explore the biological function and regulatory mechanism of MAPK1 in sepsis-induced AKI. In our study, MAPK1 exhibited high expression in the serum of AKI patients. Functionally, knockdown of MAPK1 suppressed inflammatory response, cell apoptosis in response of lipopolysaccharide (LPS) induction in HK-2 cells. Moreover, MAPK1 deficiency alleviated renal inflammation, renal dysfunction, and renal injury in vivo. Mechanistically, MAPK1 could activate the downstream p38/NF-κB pathway. Moreover, long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) was identified to serve as a competing endogenous RNA for miR-212-3p to regulate MAPK1. Finally, rescue assays indicated that the inhibitory effect of KCNQ1OT1 knockdown on inflammatory response, cell apoptosis and p38/NF-κB pathway was reversed by MAPK1 overexpression in HK-2 cells. In conclusion, KCNQ1OT1 aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 axis in sepsis. Therefore, KCNQ1OT may serve as a potential biomarker for the prognosis and diagnosis of AKI patients.

Keywords: Acute kidney injury; KCNQ1OT; MAPK1; ceRNA; p38/NF-κB

DOI: https://doi.org/10.1080/21655979.2021.2005987

Ann Med. 2021 Dec;53(1): 2153-2164

LINC01232 serves as a novel biomarker and promotes tumour progression by sponging miR-204-5p and upregulating RAB22A in clear cell renal cell carcinoma.

Qingling Liu, Chengbin Lei.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in the progression of various cancers, including clear cell renal cell carcinoma (ccRCC). This study aimed to investigate the expression and prognostic value of long intergenic non-protein coding RNA (LINC) 01232 in ccRCC and preliminary explore the molecular mechanism underlying the role of LINC01232 in ccRCC progression.METHODS: Tumour tissues and adjacent normal tissues of 122 patients with ccRCC were collected in this study. The levels of LINC01232, microRNA (miR)-204-5p and RAB22A were measured by quantitative real-time PCR. The proliferation, migration and invasion of ccRCC cells were detected by cell counting kit-8 assay and Transwell assay, respectively. The interaction among LINC01232, miR-204-5p and RAB22A was confirmed by bioinformatics analysis, dual-luciferase reporter assay and Pearson correlation analysis. The association of LINC01232 and miR-204-5p with ccRCC patient survival was verified by the Kaplan-Meier method and log-rank test. The prognostic value of LINC01232 in ccRCC was confirmed by Cox regression analysis.
RESULTS: LINC01232 expression was increased in ccRCC tumour tissues and ccRCC cells and independently predicted the prognosis of ccRCC patients. In addition, LINC01232 silencing inhibited ccRCC cell proliferation, migration and invasion. Moreover, LINC01232 served as a sponge for miR-204-5p, and miR-204-5p reduction reversed the inhibitory effect of LINC01232 silencing on ccRCC cell function. Furthermore, LINC01232 could sponge miR-204-5p, causing the elevation of RAB22A in ccRCC, thereby promoting ccRCC cell function.
CONCLUSION: LINC01232 may be an independent prognostic biomarker in ccRCC and plays an oncogenic role in ccRCC progression by sponging miR-204-5p and upregulating RAB22A.

Keywords: LINC01232; RAB22A; clear cell renal cell carcinoma; miR-204-5p; prognosis

DOI: https://doi.org/10.1080/07853890.2021.2001563

Ann Transl Med. 2021 Oct;9(20): 1544

Immunological perspective on the malignant progression of renal clear cell carcinoma.

Ji Liu, Wentao Zhang, Kang Lin, Wenchao Ma, Wei Li, Xudong Yao.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common malignancy affecting the kidneys, accounting for approximately 75% of all kidney tumors. Recently, the impact of immune response, immunotherapy, and immune-related genes (IRGs) on tumor development has received much attention. This study sought to establish a reliable immunological signature and further explore whether this signature has prognostic significance in ccRCC patients.Methods: Differentially expressed IRGs in 611 patients with diagnosis of ccRCC from The Cancer Genome Atlas (TCGA) were analyzed along with the corresponding survival time and disease clinical data. Survival analysis, selection operator Cox analysis, and minimum absolute shrinkage were applied to establish an IRG prognostic signature (IRGPS). The expression levels of relevant genes were detected by real-time quantitative PCR. A Nomogram was used to explore the possible impact of the IRGPS on the immune system, prognosis, and metastasis, and the associated mechanisms were explored through functional enrichment analysis.
Results: An IRGPS was established based on eight prognostic IRGs and was found to be closely associated with immune levels, metastasis, and prognosis. The IRGPS was determined to be a valid predictor of the efficacy of immune checkpoint inhibitors (ICIs). Three Nomograms based on the IRGPS and other clinical features were developed and could effectively predict prognosis, distant metastasis, and lymph node metastasis in patients with ccRCC.
Conclusions: The IRGPS constructed in this study serves as a tool for assessing immune status, developing individualized treatment regimens, and predicting prognosis in patients with ccRCC.

Keywords: Tumor immune microenvironment; clear cell renal cell carcinoma (ccRCC); immune checkpoint inhibitors; long non-coding RNA (lncRNA)

DOI: https://doi.org/10.21037/atm-21-4973