Hsa_circ_0088036 promotes nonsmall cell lung cancer progression by regulating miR‐1343‐3p/Bcl‐3 axis through TGFβ/Smad3/EMT signaling

Abstract

Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer‐related mortality worldwide. Circular RNAs (circRNAs) have been the focus of numerous studies, and some circRNAs have been linked to the development of multiple malignant tumors, including NSCLC. Nevertheless, the functional role and mechanisms of circRNAs in NSCLC remain largely unknown. The primary objective of this study was to screen the associated circRNA in NSCLC and investigate its mechanism. CircRNA microarray was used to identify circRNAs that were abnormally expressed in NSCLC tissue samples. Expression of hsa_circRNA_0088036 was validated in NSCLC tissues and cell lines after the correlation between hsa_circRNA_0088036 and prognosis was determined. We then used a series of function gain‐and‐loss assays to determine the role of hsa_circ_0088036 in NSCLC progression. RNA‐binding protein immunoprecipitation (RIP), RNA pull‐down, and RNA interference assays were used to assess the interaction between hsa_circ_0088036 and miR‐1343‐3p/Bcl‐3 axis. Moreover, mechanistic assays were applied to investigate the involved signaling pathway regulated by the hsa_circ_0088036/miR‐1343‐3p/Bcl‐3 axis. Microarray analysis and reverse transcription polymerase chain reaction confirmed the presence of a circRNA termed hsa_circ 0088036 that was upregulated in NSCLC tissue samples and cell lines and indicated a positive association with patient prognosis. Functionally, hsa_circ_0088036 silencing inhibited proliferative, invasive, and migrative potential of NSCLC cells as well as epithelial‐mesenchymal transition (EMT)‐related proteins by sponging miR‐1343‐3p to inhibit Bcl‐3. Furthermore, mechanistic experiments demonstrated that hsa_circ_0088036 promoted NSCLC progression by activating the TGFβ/Smad3/EMT signaling pathway via miR‐1343‐3p/Bcl‐3 axis. In conclusion, hsa_circ_0088036 functions as an oncogene by targeting the miR‐1343‐3p/Bcl‐3 axis via TGFβ/Smad3/EMT signaling pathway.

Roles and mechanisms of circular RNA in respiratory system cancers

“…Consistently, Ge et al. ( 104 ) discovered that hsa-circ-0088036 silencing upregulated miR-1343–3p, inhibiting anti apoptotic protein 3 (Bcl-3) and NSCLC proliferation, invasion, and EMT. In this regard, hsa-circ-0088036 promotes NSCLC progression and metastasis and can function as an effective target for NSCLC treatment.…”

CircRNAs: Pivotal modulators of TGF-β signalling in cancer pathogenesis

“…Researchers showed that knocking down hsa_circ_0088036 reduced the migration and invasion, proliferation of NSCLC cells and proteins involved in the EMT. It also accelerated NSCLC advancement by stimulating the TGFβ/Smad3/EMT signalling cascade via the miR-1343–3p/Bcl-3 axis [ 113 ].…”

Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age

“…This is supported by studies reporting specific micro-RNAs that target BCL3 to ameliorate cancer hallmarks. These include mir125b in ovarian cancer [ 140 ], mir627-5p in hepatocellular carcinoma [ 141 , 142 ], mir216a-3p in choliangiocarcinoma [ 143 ] and miR1343-3p in non-small cell lung cancer [ 144 ].…”