Knockdown of HSDL2 inhibits lung adenocarcinoma progression via down-regulating AKT2 expression

Abstract

The aims of the present study are to investigate the role of hydroxysteroid dehydrogenase-like 2 (HSDL2) in the progression of lung adenocarcinoma and illuminate the underlying molecular mechanisms. ShRNA targeting HSDL2 gene (siHSDL2) was utilized to knockdown (KD) HSDL2 expression. In vitro and in vivo experiments were carried out to investigate the effect of siHSDL2 on the progression of lung adenocarcinoma. Microarray hybridization and gene expression analysis were used to investigate effect of siHSDL2 on mRNA expression profile in lung cancer cell line H1299. Our data demonstrated that HSDL2 was up-regulated in lung adenocarcinoma tissue samples (P<0.001). Patients with high HSDL2 expression in cancer tissues had a worse overall survival (P<0.001). HSDL2 KD not only inhibited the proliferation, cell cycle, apoptosis, clone-formation, invasion and migration of lung adenocarcinoma cells in vitro (P<0.05), but also suppressed the growth and metastasis in vivo (P<0.05). HSDL2 KD resulted in up-regulation of 681 genes and down-regulation of 276 genes. HSDL2 KD down-regulated the protein expression and phosphorylation of protein kinase B β (AKT2) (P<0.001 and P<0.001, respectively) and protein expression of baculoviral IAP repeat-containing 3 (BIRC3; P=0.001), and up-regulated the phosphorylation of ERK (P<0.001). Rescue experiments showed that AKT2 overexpression reversed the suppression effect of siHSDL2 on cell proliferation (P<0.001), invasion (P<0.001) and migration (P<0.001) significantly. HSDL2 functions as an oncogene to promote the growth and metastasis of lung adenocarcinoma via promoting the expression of AKT2.

Construction of a B cell-related gene pairs signature for predicting prognosis and immunotherapeutic response in non-small cell lung cancer

“…Then, the functional enrichment analysis revealed that immune-activating pathways were significantly enriched in low-risk NSCLC patients, whereas high-risk NSCLC patients were closely implicated in cell proliferation related functions. Indeed, several important BRGs found in BRGPs signature, such as BIRC3, IFT57, GADD45B and SPAG4, have been associated with the proliferation or migration of NSCLC cells (41,42,(58)(59)(60)(61). Therefore, high-risk NSCLC patients are more likely to harbor genome instability status and associated with high TMB, tumor progression, and relative advanced tumor stage.…”

HSDL2 Acts as a Promoter in Pancreatic Cancer by Regulating Cell Proliferation and Lipid Metabolism

“…For example, the promotion effect of HSDL2 on the progression of lung adenocarcinoma cells depended on the AKT2 expression level. 11 In bladder cancer HSDL2 plays an oncogenic role. 12 And in human ovarian cancer HSDL2 knockdown inhibited cell proliferation, colony formation, motility and tumorigenesis.…”

MiR-26a-5p regulates proliferation, apoptosis, migration and invasion via inhibiting hydroxysteroid dehydrogenase like-2 in cervical cancer cell

“…The high expression of HSDL2 was presented in breast cancer tissues, related to high histological grades, late clinical stages and lower overall survival, even depletion of HSDL2 inhibited proliferation and induced cell cycle arrest in breast cancer [16]. Shi's researches suggested that HSDL2 was upregulated in the lung adenocarcinoma tissue and HSDL2 knockdown inhibited lung adenocarcinoma progression via downregulating AKT2 expression [17]. HSDL2 was in highly expressed in human ovarian cancer and was positively correlated with tumor progression and lymphatic metastasis, meanwhile, HSDL2 knockdown inhibited tumorigenesis in vivo or vitro [20].…”

“…Hydroxysteroid dehydrogenases like 2 (HSDL2) locates in 9q32, includes 12 exons and ubiquitously expresses in fat, liver and other tissues. Numerous studies had shown that the HSDL2 was a key factor of fatty acid regulatory in lipid metabolism [14] and abnormal HSDL2 expression was associated with a variety of cancers, such as bladder cancer [15], breast cancer [16], lung adenocarcinoma [17], thyroid carcinoma [18], cholangiocarcinoma [19], ovarian cancer [20], gliomas [21], pancreatic cancer [14] et al A large number of studies had shown that abnormal lipid metabolism could accelerate/decelerate the progression of CC [22]. HSDL2 regulated lipid metabolism, and abnormal expression of HSDL2 could promote the malignant characteristics of tumors [14,[23][24][25], including CC [23].…”