Hsa_circ_0010235 functions as an oncogenic drive in non-small cell lung cancer by modulating miR-433-3p/TIPRL axis

Abstract

Background Non-small cell lung cancer (NSCLC) is a threat to human health. Circular RNAs (circRNAs) have been proved to function in NSCLC development. In this study, the role of circRNA hsa_circ_0010235 in NSCLC progression and the possible molecular mechanism were explored. Methods Expression of hsa_circ_0010235, miRNA (miR)-433-3p and TOR signaling pathway regulator-like (TIPRL) was examined by quantitative real-time PCR (qRT-PCR). Cell viability and clonogenicity were detected by cell counting kit-8 (CCK-8) assay and colony formation assay, respectively. Flow cytometry was performed to monitor cell apoptosis and cell cycle distribution. Western blot assay was employed to evaluate the protein levels of TIPRL, light chain 3 (LC3)-II/I and p62. Cell metastasis was assessed by Transwell and wound healing assays. The targeted relationship between miR-433-3p and hsa_circ_0010235 or TIPRL was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, the role of hsa_circ_0010235 in vivo was investigated by xenograft assay. Results Hsa_circ_0010235 and TIPRL were highly expressed in NSCLC tissues and cells, while miR-433-3p was downregulated. Depletion of hsa_circ_0010235 or gain of miR-433-3p repressed proliferation and autophagy but promoted apoptosis in NSCLC cells. Hsa_circ_0010235 sponged miR-433-3p to upregulate TIPRL expression, so as to affect NSCLC development. Hsa_circ_0010235 knockdown also blocked tumor growth in vivo. Conclusion Hsa_circ_0010235 knockdown suppressed NSCLC progression by regulating miR-433-3p/TIPRL axis, affording a novel mechanism of NSCLC progression.

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer

“…17,[38][39][40][41] CircRNAs indirectly increase the expression levels of downstream target gene mRNAs and proteins by adsorbing miRNAs and participate in the occurrence and development of tumors. [42][43][44][45][46] Xu et al found that hsa-circ-000984 was mainly concentrated in the cytoplasm and identified the downstream target as miR-106b, indicating that hsacirc-000984 can act as a ceRNA by competitively binding miR-106b, increasing the expression of cyclin-dependent kinase 6 (CDK6) and participating in the proliferation and metastasis of CRC. It is worth noting that the high expression of hsa-circ-000984 is significantly related to TNM staging and the cell cycle.…”

Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

“…Increasing evidence has shown that many circRNAs (such as circ_010763, circ_001010, and circ_0078767) can affect lung cancer progression 22–24 . As a circRNA, circ_0010235 has previously been found to be overexpressed in lung cancer cells and tissues, and depletion of circ_0010235 limited the proliferation and autophagy and contributed to apoptosis in lung cancer cell lines through regulation of miR‐433‐3p/TIPRL axis 13 . In line with this research, an increase of circ_0010235 expression was also found in lung cancer cells and tissues, and circ_0010235 silencing repressed lung cancers cell growth and invasion and induced cell apoptosis.…”

“…A previous study showed that circ_0010235 acted as a tumor promoter in lung cancer. 13 However, the function of circ_0010235 in lung cancer immune response has not been reported, and its mechanism has not yet been fully established.…”

CircRNA circ_0008037 facilitates tumor growth and the Warburg effect via upregulating NUCKS1 by binding to miR‐433‐3p in non‐small cell lung cancer

“…The study by Zhang et al manifested that hsa_circ_0010235 downregulation facilitated NSCLC cell apoptosis and repressed NSCLC cell autophagy and proliferation by decreasing TIPRL expression via releasing miR‐433‐3p. 17 Also, circMED13L_012 elevated MAPK8 expression through adsorbing miR‐433‐3p, thus elevating cell chemoresistance and promoting metastasis and invasion in NSCLC. 16 Accordingly, we inferred that circ_0008037 regulated NSCLC cell proliferation, migration, invasion, and the Warburg effect through adsorbing miR‐433‐3p.…”

“… 14 Recent studies have exposed the inhibitory effect of miR‐433‐3p on NSCLC progression. 15 , 16 , 17 However, the dysregulation of miR‐433‐3p in NSCLC has not been fully explained.…”