Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In the development of liver fibrosis, some lncRNAs regulate diverse cellular processes by acting as competing endogenous RNAs (ceRNAs) and binding proteins. Previous investigations demonstrated that overexpression of lncRNAs such as H19, maternally expressed gene 3 (MEG3), growth arrest-specific transcript 5 (GAS5), Gm5091, NR_002155.1, and HIF 1alpha-antisense RNA 1 (HIF1A-AS1) can inhibit the progression of liver fibrosis. Furthermore, the upregulation of several lncRNAs [e.g., nuclear paraspeckle assembly transcript 1 (NEAT1), hox transcript antisense RNA (Hotair), and liver-enriched fibrosis-associated lncRNA1 (lnc-LFAR1)] has been reported to promote liver fibrosis. This review will focus on the functions and mechanisms of lncRNAs, the lncRNA transcriptome profile of liver fibrosis, and the main lncRNAs involved in the signalling pathways that regulate hepatic fibrosis. This review provides insight into the screening of therapeutic and diagnostic markers of liver fibrosis.

The Roles and Mechanisms of lncRNAs in Liver Fibrosis

Long non-coding RNAs: Biogenesis, functions, and clinical significance in gastric cancer

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of gene expression and physiological processes. LncRNAs are a class of ncRNAs of 200 nucleotides in length. HOX transcript antisense RNA (HOTAIR), a trans-acting lncRNA with regulatory function on transcription, can repress gene expression by recruiting chromatin modifiers. HOTAIR is an oncogenic lncRNA, and numerous studies have determined that HOTAIR is highly upregulated in a wide variety of human cancers. In this review, we briefly summarize the impact of lncRNA HOTAIR expression and functions on different human solid tumors, and emphasize the potential of HOTAIR on tumor prognosis and therapy. Here, we review the recent studies that highlight the prognostic potential of HOTAIR in drug resistance and survival, and the progress of therapies developed to target HOTAIR to date. Furthermore, targeting HOTAIR results in the suppression of HOTAIR expression or function. Thus, HOTAIR knockdown exhibits great therapeutic potential in various cancers, indicating that targeting lncRNA HOTAIR may serve as a promising strategy for cancer therapy. We also propose that preclinical studies involving HOTAIR are required to provide a better understanding of the exact molecular mechanisms underlying the dysregulation of its expression and function in different human cancers and to explore effective methods of targeting HOTAIR and engineering efficient and targeted drug delivery methods in vivo.

/pdf/lncrna-hotair-a-potential-prognostic-factor-and-therapeutic-nsev8vtil5.pdf

LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers.

Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.

Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance.

Gastric cancer (GC) is one of the major public health concerns. Long non-coding RNAs (lncRNAs) have been increasingly demonstrated to possess a strong correlation with GC and play a critical role in GC occurrence, progression, metastasis and drug resistance. Many studies have shed light on the understanding of the underlying mechanisms of lncRNAs in GC. In this review, we summarized the updated research about lncRNAs in GC, focusing on their roles in Helicobacter pylori infection, GC metastasis, tumor microenvironment regulation, drug resistance and associated signaling pathways. LncRNAs may serve as novel biomarkers for diagnosis and prognosis of GC and potential therapeutic targets. The research gaps and future directions were also discussed.

/pdf/the-multifaceted-role-of-long-non-coding-rna-in-gastric-2bn9a3sitf.pdf

The Multifaceted Role of Long Non-Coding RNA in Gastric Cancer: Current Status and Future Perspectives.

Prognostic significance of pretreatment serum carcinoembryonic antigen levels in gastric cancer with pathological lymph node-negative: A large sample single-center retrospective study

Objective
To explore the risk factors and prognosis of No.8p lymph node metastasis in cases with advanced gastric cancer. 


Methods
Clinicopathological and follow-up data of 790 cases with advanced gastric cancer undergoing gastrectomy (including No.8p lymphadenectomy) from October 2003 to October 2013 in Fujian Provincial Tumor Hospital were analyzed retrospectively. Patients receiving neoadjuvant chemotherapy were excluded. Associations of No.8p lymph node metastasis with clinicopathological characteristics and metastasis in other regional lymph node were analyzed. Prognostic difference between positive No.8p group and negative No.8p group was examined. 


Results
Positive No.8p lymph node was found in 93 cases (11.8%) among 790 cases with advanced gastric cancer. Univariate analysis showed that gender [male 9.8% (56/572) vs. female 17.0% (37/218) , P = 0.005] , preoperative CEA level [< 5 μg/L 28.0%(61/218) vs. ≥ 5 μg/L 5.6%(32/572) , P= 0.005], tumor size [diameter < 5 cm 3.8% (13/346) vs. ≥5 cm 18.0% (80/445) , P = 0.000] , tumor location [gastric fundus and cardiac 10.7% (26/244) vs. gastric body 13.5% (30/222) vs. gastric antrum 10.1% (31/308) vs. total gastric 37.5%(6/16) , P = 0.007] , Borrmann staging [typeⅡ 1.9%(4/211) vs. type Ⅲ 11.6% (54/464) vs. type Ⅳ 30.4% (35/115) , P = 0.000], tumor differentiation [high 0/8 vs. moderate 6.7%(25/372) vs. low 16.6%(68/410) , P= 0.000], T staging [T2 2.4%(4/170) vs. T3 13.1%(35/267) vs. T4 15.3%(54/353) , P = 0.000], N staging [N0 0 (0/227) vs. N1 2.2%(5/223) vs. N2 15.2%(26/171) vs. N3 36.7%(62/169) , P = 0.000] were closely associated with the No.8p lymph node metastasis. Multivariate analysis that revealed gender (OR = 1.762, 95%CI: 1.020-3.043) , tumor size (OR= 1.107, 95%CI: 1.020-1.203) , N staging (OR = 4.093, 95% CI: 2.929-5.718) , tumor differentiation (OR = 1.782, 95% CI: 1.042-3.049) , and metastasis in No.8a (OR = 5.370, 95%CI: 3.425-8.419) , No.3 (OR = 1.127, 95%CI: 1.053-1.206) , No.6 (OR = 1.221, 95%CI: 1.028-1.450) , No.7 (OR = 2.149, 95%CI: 1.711-2.699) , No, 11p (OR = 2.085, 95% CI: 1.453-2.994) , No.14v (OR = 2.604, 95% CI: 1.038-6.532) group lymph nodes were the independent risk factors of No.8p lymph node metastasis. One-year, 3-year and 5-year survival rates in positive No.8p group were 85.7% , 47.5% and 22.6% , and those in negative No.8p group were 96.2%, 82.5% and 70.3% respectively, whose differences were significant (χ2 = 109.767, P < 0.05). 


Conclusions
Metastasis in Np.8p lymph nodes is an important factor affecting the prognosis of patients with advanced gastric cancer. In patients with female gender, tumor diameter ≥5 cm, preoperative late N staging, low tumor differentiation or metastasis in No.8a, No.3, No.6, No.7, No.11p, No.14v group lymph nodes, thorough clean rance of No.8p group lymph node should be considered.


Key words: 
Stomach neoplasms, advanced; Lymph node metastasis; No.8p lymph node; Prognosis

Analysis of risk factors and prognosis of No.8p lymph node metastasis in cases with advanced gastric cancer

Objective
To evaluate the clinicopathologic characteristics and prognostic difference of gastric stump cancer between non-anastomotic site and anastomotic site.


Methods
Clinicopathologic data of 149 patients with gastric stump cancer undergoing operation (radical resection and palliative resection) in our department from January 1999 to June 2015 were analyzed retrospectively. Gastric stump cancer was defined as a primary carcinoma detected in the remnant stomach more than 5 years after subtotal gastrectomy for a benign disease (87 cases) or over 10 years after radical subtotal gastrectomy for a malignant disease (62 cases). Patients were divided into the anastomotic site group (72 cases) and the non-anastomotic site group (77 cases) according to tumor sites within the remnant stomach. Clinicopathologic characteristics, operative data, lymph node metastasis and prognosis were compared between the two groups.


Results
Compared with non-anastomotic site group, the T stage, N stage and TNM stage were later in the anastomotic site group. Number of case of T1, T2, T3, and T4 stage in anastomotic site group was 1 (1.4%) , 2 (2.8%) , 17 (23.6%) and 52 (72.2%) , while such number in non-anastomotic site group was 8 (10.4% ) , 10 (13.0%) , 27 (35.1%) and 32 (41.6%) respectively (χ2= 17.665, P= 0.001). Number of case of N0, N1, N2, and N3 in anastomotic site group was 28 (38.9%) , 10 (13.9%) , 23 (31.9%) and 11 (15.3%) , while such number in non-anastomotic site group was 55 (71.4%) , 10 (13.0%) , 7 (9.1%) and 5 (6.5%) respectively (χ2 = 19.421, P = 0.000). Number of case of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ in anastomotic site group was 3 (4.2%) , 10 (13.9%) , 47 (65.3%) and 12 (16.7%) , while such number in non-anastomotic site group was 16 (20.8%) , 40 (51.9%) , 15 (19.5%) and 6 (7.8%) respectively (χ2= 45.294, P= 0.000). The histology and Borrmann classification were worse in anastomotic site group. Anastomotic site group had 19 cases (26.4%) of good differentiation and 53 cases (73.6%) of bad differentiation, while non-anastomotic site group had 43 cases (55.8%) of well-differentiated and 34 cases (44.2%) of poorly-differentiated tumors respectively (χ2 = 13.287, P= 0.000). Anastomotic site group had 3 cases (4.2%) of Borrmann Ⅰ, 17 cases (23.6%) of Borrmann Ⅱ, 47 cases (65.3%) of Borrmann Ⅲ and 5 cases (6.9%) of Borrmann Ⅳ, while non-anastomotic site group had 18 cases (23.4%) of BorrmannⅠ, 16 cases (20.8%) of BorrmannⅡ, 34 cases (50.6% ) of Borrmann Ⅲ and 4 cases (5.2% ) of Borrmann Ⅳ respectively (χ2 = 11.445, P = 0.010). Compared with non-anastomotic site group, anastomotic site group had a lower curative resection rate [63.9% (46/72) vs. 89.6% (69/77) , χ2 = 13.977, P = 0.000] , a higher combined organ resection rate [33.3% (24/72) vs. 16.9% (13/77) , χ2= 5.394, P= 0.020] and a more metastatic lymph nodes (4.3 ± 4.9 vs. 1.9 ± 3.6, t = 3.478, P= 0.000). The lymph node metastasis rates of No.4, No.10 and jejunal mesentery root lymph node in anastomotic site group and non-anastomotic site group were 15.3% (11/72) and 5.2% (4/77) (χ2= 4.178, P= 0.041) , 9.7% (7/72) and 1.3% (1/77) (χ2= 5.196, P= 0.023) , and 25.0% (18/72) and 3.9% (3/77) (χ2 = 13.687, P= 0.000) , respectively. Median followed up of all the patients was 37 (2 to 154) months and the overall 5-year survival rate was 44.1%. The 5-year survival rate was 33.1% in anastomotic site group and 55.2% in non-anastomotic site group, and the difference was statistically significant between two groups (P = 0.015). In the subgroup analysis according to the histology differentiation, the 5-year survival rate of patients with well-differentiation was not significantly different between two groups (43.7% vs. 56.2% , P = 0.872) , but the 5-year survival rate of patients with bad differentiation in anastomotic site group was significantly lower than that in non-anastomotic site group (29.8% vs. 53.8%, P = 0.029).


Conclusion
Gastric stump cancer locating in anastomotic site indicates worse differentiation histology, higher lymph node metastasis rate, lower curative resection rate and poorer prognosis.


Key words: 
Gastric stump cancer; Tumor location; Lymph node metastasis; Prognosis

[Study on the clinicopathologic characteristics and prognostic difference of gastric stump cancer between non-anastomotic site and anastomotic site].

HOTAIR, a well-known long noncoding RNAs (lncRNA), has been recognized to contribute to the tumor metastasis in several tumors. But its role in gastric cancer remains elusive. Here, we reported an increase in HOTAIR promoted proliferation and metastasis of gastric cancer cell lines. The HOTAIR and miR-126 level was determined in 15 paired primary gastric cancer tissues and their adjacent noncancerous gastric tissues. Over-expression or downregulation HOTAIR was conducted in AGS or BGC-823 cells to investigate the impact of HOTAIR in proliferation and metastasis. Then dual luciferase reporter assay was utilized to study the interaction between CXCR4 and miR-126. Cells transfected with shHOTAIR or miR-126 mimic were subjected to western blot to investigate the role of SDF-1/CXCR4 signaling in HOTAIR mediated proliferation and metastasis. HOTAIR was highly expressed in gastric cancer tissues and several gastric cancer cell lines. Overexpressed HOTAIR facilitated proliferation and metastasis in vitro while HOTAIR knockdown inhibit proliferation and metastasis. A negative correlation was observed between miR-126 and HOTAIR. And, we also confirmed the decrease in miR-126 in clinic specimen. Furthermore, HOTAIR and miR-126 negatively regulated each other and then increase or decrease CXCR4 expression and downstream pathway, respectively. CXCR4 was confirmed as a direct target of miR-126. Our study demonstrated that high HOTAIR expression promote proliferation and metastasis in gastric cancer via miR-126/CXCR4 axis and downstream signaling pathways.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.1302

lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway.

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Prognostic significance of pretreatment serum carcinoembryonic antigen levels in gastric cancer with pathological lymph node-negative: A large sample single-center retrospective study

Analysis of risk factors and prognosis of No.8p lymph node metastasis in cases with advanced gastric cancer

[Study on the clinicopathologic characteristics and prognostic difference of gastric stump cancer between non-anastomotic site and anastomotic site].

lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway.