<p>Circ_0032821 Facilitates Gastric Cancer Cell Proliferation, Migration, Invasion and Glycolysis by Regulating MiR-1236-3p/HMGB1 Axis</p>

Abstract

Background: Circular RNAs (circRNAs) play an essential role in the pathogenesis of malignant tumors, including gastric cancer (GC). However, the effect of circ_0032821 on GC remains largely unknown. Methods: QRT-PCR assay was employed to examine the levels of circ_0032821, CEP128 mRNA and miR-1236-3p. RNase R digestion assay was utilized to verify the feature of circ_0032821. Cell Counting Kit-8 (CCK-8) assay and transwell assay were adopted to evaluate cell proliferation and metastasis. The level of glycolysis was evaluated through detecting ECAR, OCR, lactate production, glucose uptake and ATP synthesis. Dualluciferase reporter assay and RIP assay were conducted to analyze the relationship between miR-1236-3p and circ_0032821 or HMGB1. Western blot assay was adopted for high mobility group box 1 (HMGB1) level. Murine xenograft model assay was utilized for the effect of circ_0032821 in vivo. Results: High level of circ_0032821 was observed in GC tissues and cells. Silencing of circ_0032821 markedly repressed cell proliferation, metastasis and glycolysis in GC cells in vitro and blocked tumorigenesis of GC in vivo. For mechanism analysis, circ_0032821 was identified as the sponge of miR-1236-3p and HMGB1 was the target gene of miR-1236-3p. Moreover, miR-1236-3p suppression restored the influences of circ_0032821 deficiency on GC cell proliferation, metastasis and glycolysis. Overexpression of miR-1236-3p relieved the malignant behaviors of GC cells by targeting HMGB1. Conclusion: Circ_0032821 accelerated GC development through elevating HMGB1 expression via sponging miR-1236-3p.

The Elevated Circ_0067835 Could Accelerate Cell Proliferation and Metastasis via miR-1236-3p/Twist2 Axis in Hepatocellular Carcinoma

“…And we found 4 miRNAs were reported in other literatures among that, which were miR-377-5p, miR-324-5p, miR-545-3p, and miR-1236-3p, then we detected the expressions in tissue samples. No significant differences were found in miR-377-5p, miR-324-5p, and miR-545-3p (Figures 3(a) – 3(c) ), while miR-1236-3p was significant downexpressed in HCC samples ( Figure 3(d) ), which had been reported to regulate the development of various cancers [ 22 – 24 , 28 , 29 ], such as gastric cancer, lung cancer, colorectal cancer, prostate cancer, etc. Furthermore, miR-1236-3p in patients with metastasis was much lower than those without nonmetastasis ( Figure 3(e) ), and miR-1236-3p in patients with larger tumor size ( ≥5 cm, n = 35) was lower than those in patients with smaller tumor size (<5 cm, n = 21) ( Figure 3(f) ).…”

“…And it had been verified by luciferase reporter assay in HCC cells. Recent evidence manifested that miR-1236-3p was involved in some digestive system cancers, such as gastric cancer [ 22 , 23 ] and colorectal cancer [ 24 ], but the roles in HCC were little known. And current results illustrated that upregulation of miR-1236-3p could obviously restrain capacities of cell proliferation and migration.…”

“…miR-NAs may regulate various functions through binding with the 3′ untranslated regions (UTR) of downstream target genes in HCC [18][19][20][21]. miR-1236-3p has been demonstrated to be involved with some digestive system cancers, such as gastric cancer [22,23] and colorectal cancer [24]. However, the functions of miR-1236-3p in HCC also remained unclear.…”

High-Mobility Group Box 1 Overexpression Predicts a Poor Prognosis and Promotes Epithelial-Mesenchymal Transition in Gastric Cancer by Activating TLR4/NF-κB Signaling

“…However, there is currently no consensus on the underlying mechanisms by which high HMGB1 expression leads to poor prognosis in patients with GC. MiR-129-5p, miR-1179, and miR-1236-3p have been identified as upstream molecules that regulate the aberrant expression of HMGB1 [23][24][25]. Huang et al [26] proposed that HMGB1 is involved in the HMGB1/FBXW7 signaling axis, leading to peritoneal metastasis in patients with GC.…”

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

“…Gastric carcinoma (GC) is the fourth most common cancer and the second most common cause of cancer death, and many circRNAs have been studied with a regulatory role in GC. CircNRIP1 can activate AKT1/mTOR pathway by sponging miRNA-149-5p [52], circRNA-100290 up-regulates EMT-related oncogene ITGA11 by sponging miR-29b-3p [53], circ-0032821 can regulate miR-1236-3p/HMGB1 axis [54], and circ_0005529 up-regulates SP1 by sponging miR-527 [55], thus promoting the proliferation, EMT, migration and invasion of GC cells. Circ-OXCT1 suppresses EMT and metastasis by attenuating the TGF-beta pathway through the circ-OXCT1/miR-136/SMAD4 axis [56], circRNA-0005075 suppresses carcinogenesis via regulating miR-431/p53/EMT [57], circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1 [58], hsa_circ_0007967 promotes gastric cancer proliferation through the miR-411-5p/MAML3 axis [59], the circular RNA, circ_0006089, also regulates the IGF1R expression by targeting miR-143-3p to promote gastric cancer proliferation, migration, and invasion [60], the overexpression of circ_0051620 is associated with progress and poor prognosis of GC, promoting the development and metastasis via sponging miR-338-3p and decoying ADAM17 [61], and circFGD4 can inactivate β -catenin signal through miR-532-3p/APC pathway to inhibit the activity, migration, and EMT of GC cells [62].…”