<p>Emerging Roles Of hsa-circ-0046600 Targeting The miR-640/HIF-1α Signalling Pathway In The Progression Of HCC</p>

Abstract

Purpose: Circular RNAs (circRNAs) play important roles in the development and progression of various human cancers. hsa-circ-0046600 is a circRNA of unknown function. The purpose of this study was to investigate the biological function of hsa-circ-0046600 in hepatocellular carcinoma (HCC) and elucidate the possible molecular mechanisms of this circRNA. Materials and methods: GSE97332, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the expression of hsa-circ-0046600 in HCC tissues and cells. A dual-luciferase reporter assay was used to confirm the interaction between hsa-circ-0046600 and miR-640, and a metaanalysis confirmed the expression of miR-640 in HCC. Bioinformatics was used for the functional analysis of miR-640 target genes. N-cadherin and HIF-1α expression was measured by Western blot analysis. Results: The expression level of hsa-circ-0046600 in HCC tissue was significantly higher than that in adjacent normal tissue (P < 0.05) and was associated with tumour size, TNM stage and pathological vascular invasion. Moreover, the downregulated expression of hsacirc-0046600 significantly inhibited the migration of HepG2 and SK-HEP-1 cells. hsa-circ-0046600 is present mainly in the cytoplasm and promotes the expression of proteins such as HIF-1α by competitively binding to miR-640 in HCC, thereby affecting the malignant biological behaviour of liver cancer cells. Conclusion: hsa-circ-0046600 can be used as a new biomarker for HCC diagnosis and disease progression and provides a potential target for targeted therapy.

MicroRNA‑640 promotes cell proliferation and adhesion in glioblastoma by targeting Slit guidance ligand 1

“…For example, miR-640 inhibits the formation of capillaries ( 22 ); however, its role in cancer development has not yet been investigated. In their research, Li et al ( 23 ) and Zhai et al ( 24 ) both demonstrated that miR-640 exerts tumor-suppressive effects in ovarian cancer and hepatocellular carcinoma. In another study, miR-640 was reported to enhance the development of prostate cancer ( 25 ).…”

The interplay between HIF-1α and noncoding RNAs in cancer

“…Research conducted by Chi et al suggested that circRNA cir-cPIP5K1A functions as a miR-600 sponge to inhibit miR-600 to disrupt the interaction at the 3'-UTR between HIF-1α and miR-600 to promote HIF-1α posttranscriptional expression, as well as proliferation and metastasis of non-small-cell lung cancer [130]. In addition, in hepatocellular carcinoma, circRNA_0046600 could upregulate HIF-1α by sponging miR-640 to promote cancer progression [131]. CircRNAs are a novel research focus,, so no additional studies on the regulatory roles of circRNAs in HIF-1α expression are currently available.…”

“…gallbladder cancer promotes migration, invasion and EMT post-transcriptional regulation [122] lncRNA PVT1 lung cancer promotes viability and proliferation post-transcriptional regulation [123] lncRNA HOTAIR renal cancer promotes proliferation, migration and EMT, inhibits apoptosis post-transcriptional regulation [124] lncRNA ROR hepatocellular cancer promotes viability post-transcriptional regulation [125] lncRNA NEAT1 osteosarcoma promotes proliferation and invasion post-transcriptional regulation [126] lncRNA UCA1 acute myelocytic leukemia promotes glycolysis and chemoresistance post-transcriptional regulation [127] lncRNA PVT1 gastric cancer promotes proliferation and invasion post-transcriptional regulation [128] lncRNA DANCR nasopharyngeal carcinoma promotes invasion and metastasis post-transcriptional activation via ILF3/ ILF2 [129] circPIP5K1A lung cancer promotes proliferation and metastasis post-transcriptional regulation [130] circRNA_0046600 hepatocellular carcinoma promotes migration post-transcriptional regulation [131] miR-214 lung cancer promotes invasion, proliferation and migration transcriptional activation via ING4 [132] miR-206 lung cancer inhibits proliferation and angiogenesis, promotes apoptosis transcriptional inhibition via 14-3-3ζ/STAT3 axis [133] miR-675-5p glioma promotes angiogenesis stabilize the mRNA via HuR [134] lncRNA CPS1-IT1 hepatocellular cancer inhibits EMT, proliferation, migration and invasion transcriptional inhibition via Hsp90 [135] lncRNA PVT1 gastric cancer promotes survival, inhibits apoptosis transcriptional activation via mTOR [136] has no effect on HIF-1α degeneration but acts as an adapter protein to recruit transcriptional repressors to regulate HIF activity [157]. MiR-206 can attenuate the growth and angiogenesis of non-small-cell lung cancer cells through the 14-3-3z/STAT3/HIF-1α/VEGF pathway.…”

Hsa_circ_0000345 regulates the cellular development of ASMCs in response to oxygenized low‐density lipoprotein

“…Last but not least, circRNAs and HIF‐1α also closely interact. In hepatocellular carcinoma, has‐circ‐0046600 enhanced the expression of HIF‐1α through competitive binding with miR‐640 15 . In addition, knockdown of circ_PIP5K1A suppressed HIF‐1α by promoting the sponging of miR‐600 16 .…”

“…In hepatocellular carcinoma, has-circ-0046600 enhanced the expression of HIF-1α through competitive binding with miR-640. 15 In addition, knockdown of circ_PIP5K1A suppressed HIF-1α by promoting the sponging of miR-600. 16 In summary, cir-cRNAs exerted dramatic effects on hypoxia and atherosclerosis; however, the role of circRNAs/HIF-1α in atherosclerosis needs to be further explored.…”