miR-519d-3p suppresses tumorigenicity and metastasis by inhibiting Bcl-w and HIF-1α in NSCLC

Abstract

Bcl-w, a member of the Bcl-2 family, is highly expressed in various solid tumor, including lung cancer, suggesting that it is involved in cancer cell survival and carcinogenesis. Solid cancer-induced hypoxia has been reported to increase angiogenesis, growth factor, gene instability, invasion, and metastasis. Despite many studies on the treatment of non-small cell lung cancer (NSCLC) with a high incidence rate, the survival rate of patients has not improved because the cancer cells acquired resistance to treatment. This study investigated the correlation between Bcl-w expression and hypoxia in tumor malignancy of NSCLC. Meanwhile, microRNAs (miRNAs) are involved in a variety of key signaling mechanisms associated with hypoxia. Therefore, we discovered miR-519d-3p, which inhibits the expression of Bcl-w and hypoxia-inducing factor (HIF)-1α, and found that it reduces hypoxia-induced tumorigenesis. Spearman’s correlation analysis showed that the expression levels of miR-519d-3p and Bcl-w/HIF-1α were negatively correlated, respectively. This showed that miR-519d-3p can be used as a diagnostic biomarker and target therapy for NSCLC.

Circulating microRNAs as a potential diagnostic marker in chronic pancreatitis, pancreatic cancer and colorectal cancer

“…However, there is limited research on pancreatic diseases involving this molecule. Table 3 [20][21][22][23][24][25][34][35][36][37][38][39][40][41][42] contains information on the miRNA-17-5p, miRNA-93, and miRNA-519d-3p molecules and their role in cancer in relation to the results obtained in this study. Chen et al [40] Wang et al [20] miRNA-519d-3p Expression distinguishes patients with chronic pancreatitis from healthy volunteers with sensitivity and specificity of 60% and 80%, respectively while the sensitivity and specificity of this test in distinguishing pancreatic cancer patients from healthy participants is 59% and 79%, respectively Functions as a tumor suppressor by targeting and downregulating the expression of B-Cell Lymphoma 6 Protein (BCL6) Expression significantly decreased in glioma tissues; regulation of B-Cell Lymphoma 1 Protein (CCND1) In OSCC tissues, downregulating miR-519d-3p expression correlated with a higher tumor grade, and upregulating miR-519d-3p expression inhibited OSCC cells viability and proliferation as well as increased cells in G0/G1 cell cycle Plasma expression is significantly decreased in NSCLC patients compared to healthy individuals; molecular targets of this molecule: BCL2-like protein 2 (BCL-W) and hypoxia-inducible factor 1 subunit alpha (HIF-1a): miRNA-519 and expression of BCL-W and HIF-1 a mRNA showed an inverse correlation in NSCLC HIF-1A mRNA is negatively correlated with the miR-519d-3p levels in human PDAC tissue samples; miR-519d-3p negatively regulated ribosomal protein S15a (RPS15A) expression in pancreatic cancer cells Expression is significantly decreased in pancreatic cancer tissues, which is involved in the Wnt /b-catenin signaling pathway Levels in pancreatic cancer cells were reduced following hypoxia; transfection with miR-519 mimics inhibited pancreatic cancer cells' invasiveness and induced apoptosis under hypoxic conditions; programmed death ligand 1 (PD-L1) as a target of miR-519 and rescued the miR-519 mimic-attenuated tumorigenesis of pancreatic cancer cells under hypoxic conditions; treatment with miR-519 significantly suppressed the tumor growth of pancreatic cancer cells…”

“…High levels of miR-17-5p and low levels of RBL2 protein are associated with poor prognosis [12]. The summary of molecular targets for miRNAs is in Table 1 [12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Moreover, miRNA-93-5p is involved in gemcitabine resistance in pancreatic cancer via targeting the PTEN-mediated PI3K/Akt signaling pathway [13].…”

“…In this pilot study, we have examined the expression of the above-mentioned miRNAs in the plasma of CP, PDAC, and CRC patients and correlated them with available clinical and demographic data and with markers of carcinogenesis: CA19-9 and carcinoembryonic antigen (CEA). miR-93-5p Oncogene MDR1, PTEN, CDKN1A [13,20] miR-320a Oncogene PDCD4 [14] miR-519d-3p Tumor suppressor RPS15A, BCL6, CCND1, BCL-W, HIF-1a [15,[21][22][23][24][25] miR-526b-3p Tumor suppressor E2F1, WEE1 [16,17] miR-5590 Tumor suppressor TGFb-R1, TGFb-R2, SMAD3, SMAD4 [18,19] Our study aimed to investigate the potential of selected molecules as diagnostic biomarkers. Additionally, we checked whether the examination of miRNA expression could help differentiate between CP and PDAC.…”

LIM-domain binding protein 2 was down-regulated by miRNA-96-5p inhibited the proliferation, invasion and metastasis of lung cancer H1299 cells

“…For example, miR-519d-3p suppressed tumorigenicity and metastasis by inhibiting Bcl-w and HIF-1α in NSCLC. 12 MiRNA-199 expression was down-regulated in LCa and it might inhibit the malignant progression of LCa through interacting with RGS17. 13 MiR-96-5p was reported to participate in the occurrence and development of multiple tumors, including breast cancer, 14 colon cancer, 15 gastric adenocarcinoma, 16 glioma, 17 and NSCLC.…”

RP11-79H23.3 Inhibits the Proliferation and Metastasis of Non-small-cell Lung Cancer Through Promoting miR-29c

“…It is highly aggressive which leads to distant metastasis easily at the advanced stage. Metastasis is a general complication and critical factor that leading to a remarkable shortened survival rate (Choi et al 2021 ; Jiang et al 2021b ; Yu et al 2021 ). Owing to cancer metastasis and treatment resistance, the mortality rate of NSCLC is increasing which resulting in a low five-year survival rate, only less than 15% (Wang et al 2022c ).…”