Long noncoding RNA SNHG14 accelerates cell proliferation, migration, invasion and suppresses apoptosis in colorectal cancer cells by targeting miR-944/KRAS axis through PI3K/AKT pathway
Authors: T Li
X-C Xu
Q Pei
Y Zhang
G-S Liu
H Gao
H-P Li
W Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Colorectal cancer; SNHG14; miR-944; KRAS; oncogene
Affiliations: Department of Gastroenterology Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. .

Abstract:  Objective: Colorectal cancer (CRC) is a gastrointestinal tract cancer, which threatens the well-being of million of patients due to high metastasis. Recently, numerous studies have recognized nuclear RNA host gene 14 (SNHG14) as a remarkable oncogene in different cancers. However, the regulatory mechanism of SNHG14 in CRC development is mostly unclear. Patients and methods: The expression of SNHG14, miR-944 and Kirsten rat sarcoma (KRAS) in tissues and cells was measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry assay, respectively. Cell migration and invasion were assessed using transwell assay. Protein expression of KRAS, AKT, phosphorylated AKT (p-AKT), phosphatidylinositol-3-kinase (PI3K) and phosphorylated PI3K (p-PI3K) was detected by Western blot. Animal models were constructed by subcutaneously injecting SW620 cells stably transfected with sh-SNHG14 and sh-NC. The interaction among SNHG14, miR-944 and KRAS was determined by luciferase reporter assay and RIP assay. Results: The expression of SNHG14 and KRAS was up-regulated whereas miR-944 was down-regulated in CRC tumors and cells compared with normal tissues and cells. In addition, SNHG14 silencing attenuated cell proliferation, migration and invasion, while accelerated apoptosis in CRC cells by suppressing PI3K/AKT pathway. Consistently, SNHG14 knockdown hindered tumor growth in vivo. MiR-944 was a target of SNHG14 and directly targeted KRAS. Moreover, miR-944 inhibitor abrogated silenced SNHG14-mediated inhibition on proliferation, migration and invasion, as well as promotion on apoptosis in CRC cells. Similarly, miR-944 regulated CRC cell progression by targeting KRAS through PI3K/AKT pathway. Conclusions: SNHG14 contributed to cell proliferation, migration and invasion, while suppressed apoptosis in CRC cells by targeting miR-944/KRAS axis through PI3K/AKT pathway, representing novel biomarkers for CRC therapy. 

Retracted: No

PubPeer comments:
 Fig 1.  C, Survival rate of CRC patients with high and low level of SNHG14 was analyzed. ... . F, Survival rate of CRC patients with high and low level of miR-944 was determined . Notice the death in the lower (green) trajectory in 1F at 50 months, with no matching death in either line of 1C. Conversely, 1C shows deaths in the lower (red) trajectory at 35 and 45 months, not marked in either line of 1F.  I assume that the vertical ticks along the curves (highlighted) indicate where patients become unavailable for further data collection, and are right-censored. So in 1C, the early tickmark along the green trajectory for the low-SNHG14 group means that one patient dropped out, reducing N to 13; then three deaths and three steps leave the rest of that trajectory at a survival rate of 77%. So far so good. But the tickmarks **do not match** between 1C and 1F, the same patients grouped by different criteria. Am I missing something? In 1F, there is a single early subject drop-out along the green trajectory followed by 10 steps, of different sizes, i.e. different numbers of deaths. This is not compatible with the low-miR-944 group where N=12. It is conceivable that the lines were mis-labeled, though changing the labels would completely contradict the text s conclusions. Perhaps I am over-thinking this. ,