<p>miR-335-5p Regulates Cell Cycle and Metastasis in Lung Adenocarcinoma by Targeting CCNB2</p>

Abstract

Background: Lots of studies have shown that cyclin disorders can promote tumor development. This study aims to investigate the biological function and molecular mechanism of CCNB2 in lung adenocarcinoma (LUAD). Methods: LUAD data were downloaded from GEO database and TCGA-LUAD database. Differential analysis was conducted to find the differentially expressed miRNAs and mRNAs, while targeted prediction was done for the access of potential target mRNAs. Gene expression level was detected by qRT-PCR and Western blot in human LUAD cell lines A-427, A549, Calu-3, PC-9 and human bronchial epithelial cell line BEAS-2B. MTT, colony formation, Transwell and flow cytometry assays were used to detect cell proliferation, metastasis, and cell cycle changes of PC-9 cell line. The dual-luciferase reporter gene was used to detect the targeted binding relationship of the target miRNA and mRNA. Results: CCNB2 was highly expressed and served as a biomarker indicating poor prognosis in LUAD patients. Cell function experiments confirmed the inhibitory effects of silencing CCNB2 on the proliferation, migration and invasion of LUAD cells and cell cycle was blocked in the G0/G1 phase. In addition, with regard to the regulatory mechanism, we demonstrated that miR-335-5p had binding sites with 3ʹ-UTR of CCNB2, indicating that miR-335-5p could target the regulation expression of CCNB2. In subsequent cell function tests, overexpression of miR-335-5p inhibited the proliferation and metastasis of cancer cells, and the rescue experiments also verified that miR-335-5p could reverse the promotion of CCNB2 overexpression on the progress of cancer cells. Conclusion: In summary, our results revealed that miR-335-5p could target the downregulation of CCNB2 to inhibit the occurrence and development of LUAD.

Bioinformatics Prediction and Experimental Verification Identify MAD2L1 and CCNB2 as Diagnostic Biomarkers of Rhabdomyosarcoma

“…These two genes are positively correlated with the clinical stage of tumours. Some studies reported that MAD2L1 and CCNB2 are highly expressed in gastric cancer, liver cancer, lung cancer, and other types of cancers; thus, they possibly serve as tumourpromoting genes [17,[35][36][37][38], which are consistent with our immunohistochemical results. Our results further revealed that CCNB2 expression is associated with tumour size.…”

“…CCNB2 may responsible for the initiation and progression of liver cancer through the CCNB2/PLK1 pathway and increase the growth and migration of liver cancer cells [35]. miR-335-5p can target the downregulation of CCNB2, thereby inhibiting the occurrence and development of lung adenocarcinoma [17]. In summary, the six genes predicted by our research promote the occurrence of various tumours, and may serve as the diagnostic markers of RMS.…”

“…Abnormal expression of MAD2 may be related to the pleomorphic features and atypical mitosis of soft tissue sarcomas and the progression of translocation-associated highgrade tumours [14]. The cell cycle-related molecule CCNB2 is a potential diagnostic or prognostic marker for various cancers, including liver cancer [15], melanoma [16] and lung cancer [17]. However, the clinical roles of MAD2L1 and CCNB2 in RMS are unclear.…”

Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

“…Moreover, some studies have also indicated that the six hub mRNAs could be used as promising biomarkers related to the metastasis or prognosis of cancer. For example, over-expression of BUB1B is associated with poor prognosis in patients with prostate cancer, and could promote proliferation and migration of prostate cancer cells ( 35 ); Wang et al ( 36 ) proposed that miR-335-5p could regulate metastasis of lung adenocarcinoma by targeting CCNB2. Yan et al ( 37 ) showed that KIF18B could act as a promoting factor for proliferation and metastasis of cutaneous melanoma.…”

LncRNA HCG18 Promotes Clear Cell Renal Cell Carcinoma Progression by Targeting miR-152-3p to Upregulate RAB14

“… 14 miR-335-5p overexpression suppressed the metastasis of lung adenocarcinoma cells via downregulating CCNB2 . 15 miR-152-3p was identified to act as a tumor suppressor in several cancers, such as prostate cancer and glioma. 16 , 17 Nevertheless, the biological significance of miR-152-3p in ccRCC is still obscure.…”