<p>Circular RNA circLPAR3 Facilitates Esophageal Squamous Cell Carcinoma Progression Through Upregulating HMGB1 via Sponging miR-375/miR-433</p>

Abstract

Background: Circular RNAs (circRNAs) are critical regulators of many diseases, including esophageal squamous cell carcinoma (ESCC). A recent study has shown that circLPAR3 is highly expressed in ESCC, but its role and mechanism in ESCC are still unclear. Methods: The expression levels of circLPAR3, microRNA-375 (miR-375), miR-433, and high-mobility group box 1 (HMGB1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular characteristic and localization of circLPAR3 were identified by Ribonuclease R (RNase R) and nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were tested by transwell assay. Moreover, Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related protein, as well as the HMGB1 protein. Besides, mice xenograft models were constructed to assess the effect of circLPAR3 on ESCC tumor growth in vivo. In addition, dual-luciferase reporter and RNA pull-down assays were used to identify the mechanism of circLPAR3. Results: CircLPAR3 was upregulated in ESCC tissues and cells, and its high expression was related to the poor prognosis of ESCC patients. CircLPAR3 was a stable cyclic transcript, mainly located in the cytoplasm, and its knockdown hindered the proliferation, migration and invasion of ESCC cells and inhibited ESCC tumor growth in vivo. MiR-375/miR-433 could be sponged by circLPAR3, and their inhibitors could reverse the suppression effect of silenced circLPAR3 on ESCC progression. HMGB1 could be targeted by miR-375/miR-433, and its overexpression also could invert the inhibition effect of circLPAR3 knockdown on ESCC progression. Conclusion: CircLPAR3 might play an oncogenic role in ESCC through sponging miR-375/ miR-433 to promote HMGB1 expression, which might provide a theoretical basis for circLPAR3 to become a biomarker for ESCC therapy.

CAFs-derived small extracellular vesicles circN4BP2L2 promotes proliferation and metastasis of colorectal cancer via miR-664b-3p/HMGB3 pathway

“…HMGB3 is involved in the progression of some cancers, such as esophageal squamous cell cancer, breast cancer and so on. 36 , 37 HMGB3 has been demonstrated to play an oncogene role in CRC. 38 miR-93 targeted regulated HMGB3 expression, and the repression effect of miR-93 on biological behavior of CRC cells could be counteracted by HMGB3 overexpression.…”

Downregulation of circLPAR3 inhibits tumor progression and glycolysis by liberating miR‐144‐3p and upregulating LPCAT1 in oral squamous cell carcinoma

“…Researchers reported that circLPAR3 exerted a tumor‐promoting impact through upregulating MET via binding to miR‐198 in ovarian cancer 22 and esophageal squamous cell cancer 23 . Cheng et al indicated that circLPAR3 sponged miR‐433/miR‐375 and elevated HMGB1 expression, resulting in ESCC growth 24 . Fu et al suggested that circLPAR3 was overexpressed in OSCC samples and cell lines, and circLPAR3 silencing decreased xenograft tumor growth and facilitated cell apoptosis, restrained cell proliferation, stemness, and migration through repressing HMGB2 by liberating miR‐643 19 .…”

“…23 Cheng et al indicated that circLPAR3 sponged miR-433/miR-375 and elevated HMGB1 expression, resulting in ESCC growth. 24 Fu et al…”

E2F transcription factor 1 is involved in the phenotypic modulation of esophageal squamous cell carcinoma cells via microRNA-375

“…Our further ChIP-qPCR assay validated the direct interaction between miR-375 and E2F1. Previously, miR-375 has been indicated to be regulated by circular RNA and long noncoding RNA (lncRNA) in ESCC and tongue squamous cell carcinoma, respectively [ 26 , 27 ]. However, there is little information concerning the interactions between miR-375 and transcription factors, which highlights the novelty of our research.…”