lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6

Abstract

Growing evidence have shown the important regulation of lncRNAs (long noncoding RNAs) in non–small cell lung cancer (NSCLC). lncRNA hepatocyte nuclear factor 1 homeobox A (HNF1A)‐antisense RNA 1 (AS1), an “oncogene”, was reported to regulate human tumors progression. However, the molecular mechanism of HNF1A‐AS1 involved in the development of NSCLC is still under investigation. In the current study, we found that HNF1A‐AS1 was relatively upregulated in both NSCLC patient tissues and cell lines. Functional studies established that overexpression of HNF1A‐AS1 promoted cell proliferation, cell cycle, invasion, and migration of NSCLC cells in vitro. The promotion abilities of HNF1A‐AS1 on NSCLC cell progression were suppressed via knockdown of HNF1A‐AS1. miR‐149‐5p was then proved to be a novel target of HNF1A‐AS1, whose expression was negatively correlated with HNF1A‐AS1 in NSCLC patient tissues and cell lines. HNF1A‐AS1 increased the expression of cyclin‐dependent kinase 6 (Cdk6) via sponging with miR‐149‐5p. Gain‐ and loss‐of‐functional studies indicated that HNF1A‐AS1 promoted NSCLC progression partially through inhibition of miR‐363‐3p and induction of Cdk6. Subcutaneous xenotransplanted tumor model confirmed that interference of HNF1A‐AS1 suppressed the tumorigenic ability of NSCLC via upregulation of miR‐149‐5p and downregulation of Cdk6 in vivo. In conclusion, our findings clarified the biologic significance of the HNF1A‐AS1/miR‐149‐5p/Cdk6 axis in NSCLC progression and provided novel evidence that HNF1A‐AS1 may be a new potential therapeutic target for the treatment of NSCLC.

RETRACTED ARTICLE: Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

“…Abnormal expression of HNF1A-AS1 has been reported in sundry human cancers and HNF1A-AS1 could as a tumor inducer gene or tumor suppressor gene [11]. A study has reported that restoration of HNF1A-AS1 accelerated cell proliferation, invasion, cell cycle and migration of nonsmall cell lung cancer cells in vitro [12]. Another study revealed that overexpression of HNF1A-AS1 forecasted poor prognosis for oral squamous cell carcinoma patients [13].…”

MYC‐activated lncRNA HNF1A‐AS1 overexpression facilitates glioma progression via cooperating with miR‐32‐5p/SOX4 axis

“…Substantial studies supported the crucial regulator roles of lncRNAs in the initiation, development, and progression of various diseases, including tumors 15‐17 . HNF1A‐AS1 has been reported to exhibit carcinogenesis property in gastric cancer 18 and non–small cell lung cancer 19 . In the present study, we found the aberrant overexpression of HNF1A‐AS1 in glioma cell lines, which was in accordance with HNF1A‐AS1 overexpression in urothelial carcinoma of the bladder 20 .…”

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

“…MiR‐488‐3p negatively modulates ZBTB2 and activates the p53 pathway to exert its anti‐cancer effect in ESCC . Additionally, miR‐149‐5p is downregulated in multiple tumors, such as gastric cancer, non‐small cell lung cancer, and osteosarcoma . These studies reveal that miR‐149‐5p exerts a tumor suppressor effect.…”

“…18 Additionally, miR-149-5p is downregulated in multiple tumors, such as gastric cancer, non-small cell lung cancer, and osteosarcoma. [19][20][21] These studies reveal that miR-149-5p exerts a tumor suppressor effect. Nonetheless, the role of miR-149-5p in ESCC and its mechanism remain unclear.…”